Mu opioid receptor mRNA overexpression predicts poor prognosis among 18 common solid cancers: A pan-cancer analysis.

Background: Opioids are widely used for patients with solid tumors during surgery and for cancer pain relief. We conducted a pan-cancer genomic analysis to investigate the prognostic features of Mu opioid receptor (MOR) mRNA expression across 18 primary solid cancers. Methods: All the data of cancer with MOR mRNA were retrieved from cBioPortal for Cancer Genomics. Logistic regression was used to determine the associations between MOR mRNA expression and clinicopathological features. Log-rank test and Cox regression was used for survival analysis. Subgroup analysis and propensity score matching were also carried out. Results: 7,274 patients, including 1,112 patients with positive MOR mRNA expression, were included for data analyses. Positive MOR mRNA expression was associated with more advanced stage of T (adjusted Odds ratio [OR], 1.176; 95% confidence interval [CI], 1.022-1.354; P=0.024), M (adjusted OR, 1.548; 95% CI, 1.095-2.189; P=0.013) except N (adjusted OR, 1.145; 95% CI, 0.975-1.346; P=0.101), and worse prognosis for overall survival (Hazard ratio [HR] 1.347, 95% CI 1.200-1.512, P<0.001), progression-free survival (HR 1.359, 95% CI 1.220-1.513, P<0.001), disease-free survival (HR 1.269, 95% CI 1.016-1.585, P<0.001) and disease-specific survival (HR 1.474, 95% CI 1.284-1.693, P<0.001). Patients with positive MOR mRNA expression tended to be classified as tumor microenvironment immune types II, representing low PD-L1 and low CD8A expression. Conclusion: MOR mRNA overexpression is associated with poor prognosis and poor response to PD-L1 therapy.

A new formula based on height for determining endotracheal intubation depth in pediatrics: A prospective study.

STUDY OBJECTIVE: The main objective was to devise an endotracheal intubation formula based on pediatric patients' strongly correlated growth parameters. The secondary objective was to compare the accuracy of the new formula to the age-based formula from Advanced Pediatric Life Support Course (APLS formula) and the middle finger length-based formula (MFL-based formula). DESIGN: A prospective, observational study. SETTING: Operation. PATIENTS: 111 subjects age 4-12 years old undergoing elective surgeries with general orotracheal anesthesia. INTERVENTIONS AND MEASUREMENTS: Growth parameters, including age, gender, height, weight, BMI, middle finger length, nasal-tragus length, and sternum length, were measured before surgeries. Tracheal length and the optimal endotracheal intubation depth (D) were measured and calculated by Disposcope. Regression analysis were used to establish a new formula for predicting the intubation depth. A self-controlled paired design was used to compare the accuracy of the intubation depth between the new formula, APLS formula, and MFL-based formula. MAIN RESULTS: Height (R = 0.897, P < 0.001) was strongly correlated to tracheal length and the endotracheal intubation depth in pediatric patients. New formulae basing on height were established, including new formula 1: D (cm) = 4 + 0.1 × Height (cm) and new formula 2: D (cm) = 3 + 0.1 × Height (cm). Via Bland-Altman analysis, the mean differences for new formula 1, new formula 2, APLS formula and MFL-based formula were - 0.354 cm (95% LOA, -1.289 to 1.998 cm), 1.354 cm (95% LOA, -0.289 to 2.998 cm), 1.154 cm (95% LOA, -1.002 to 3.311 cm), -0.619 cm (95% LOA, -2.960 to 1.723 cm), respectively. The rate of optimal intubation for new formula 1 (84.69%) was higher than for new formula 2 (55.86%), APLS formula (61.26%), and MFL-based formula. (69.37%). CONCLUSIONS: The prediction accuracy for intubation depth of the new formula 1 was higher than the other formulae. The new formula based on height: D (cm) = 4 + 0.1 × Height (cm) was preferable to APLS formula and MFL-based formula with a high incidence of appropriate endotracheal tube position.

Effect of head position changes on the depth of tracheal intubation in pediatric patients: A prospective, observational study.

Purpose: The purpose of this study was to investigate the effect of changing head position on the endotracheal tube (ETT) depth and to assess the risk of inadvertent extubation and bronchial intubation in pediatric patients. Methods: Subjects aged 4-12 years old with orotracheal intubation undergoing elective surgeries were enrolled. After induction, the distances between "the ETT tip and the trachea carina" (T-C) were measured using a Disposcope flexible endoscope in head neutral position, 45° extension and flexion, 60° right and left rotation. The distance of the ETT tip movement relative to the neutral position (ΔT-C) was calculated after changing the head positions. The direction of the ETT tip displacement and the adverse events including endobronchial intubation, accidental tracheal extubation, hoarseness and sore throat were recorded. Results: The ETT tip moved toward the carina by 0.5 ± 0.4 cm (P < 0.001) when the head was flexed. After extending the head, the ETT tip moved toward the vocal cord by 0.9 ± 0.4 cm (P < 0.001). Right rotation resulted that the ETT tip moved toward the vocal cord direction by 0.6 ± 0.4 cm (P < 0.001). Moreover, there was no displacement with the head on left rotation (P = 0.126). Subjects with the reinforced ETT had less ETT displacement after changing head position than the taper guard ETT. Conclusion: The changes of head position can influence the depth of the ETT especially in head extension. We recommend using the reinforced ETT to reduce the ETT displacement in pediatrics to avoid intubation complications. Clinical trial registration: [www.ClinicalTrials.gov], identifier, [ChiCTR2100042648].

Evaluation of the Effect of Dexmedetomidine on Postoperative Cognitive Dysfunction through Aß and Cytokines Analysis.

Postoperative cognitive dysfunction is a common postoperative neurological complication in elderly patients, and has some relationship with neuroinflammation. some studies have shown ability of dexmedetomidine to improve cognitive performance in elderly individuals who underwent thoracic surgery. Therefore, our study hypothesized that dexmedetomidine treatment may reduce the incidence of POCD in elderly patients.In addition,this study detected the antineuroinflammatory effects of dexmedetomidine by ß-amyloid aggregation inhibitors and release of cytokines in elderly patients . The results show that dexmedetomidine used during operation can inhibit the postoperative release of Aß and cytokines in elderly patients, and dexmedetomidine used during operation can reduce the incidence of postoperative cognitive dysfunction, with dose-dependence. These results provide a clinical application direction for clinical anesthesiologists and ICU physicians.

Dexmedetomidine alleviates pulmonary ischemia-reperfusion injury through modulating the miR-21-5p/Nr4a1 signaling pathway.

This study aims to investigate the protection of dexmedetomidine (Dex) against pulmonary ischemia-reperfusion injury (PIRI) in the mouse model and reveal the mechanism in hypoxia reoxygenation (H/R)-induced mouse pulmonary vascular endothelial cells (MPVECs). The lung wet-to-dry weight ratio, histopathological features, and malondialdehyde (MDA) concentrations were measured. The H/R-induced MPVECs were exposed to Dex, and the cell viability, cell apoptosis and protein expressions were assessed by the Cell Counting Kit-8 (CCK8) assay, flow cytometry and western blot, respectively. In addition, the regulatory relationship between miR-21-5p and orphan nuclear receptor 4A1 (Nr4a1) was revealed by several assays, including the dual-luciferase reporter assay, real-time quantitative polymerase chain reaction (RT-qPCR) and western blot. We found that the Dex treatment significantly alleviated pulmonary injury and decreased the level of MDA and wet/dry weight ratio in PIRI mice. Dex treatment also increased cell viability, reduced apoptotic ratio and downregulated expression levels of Cleaved Caspase-3 and Cleaved Caspase-9 in H/R induced MPVECs. Furthermore, the expression of miR-21-5p was upregulated, while Nr4a1 was downregulated by Dex in a concentration-dependent manner in H/R induced MPVECs. Moreover, Nr4a1 was verified as a target of miR-497-5p. Overexpression of Nr4a1 could reverse the protective effects of Dex on alleviating H/R-induced injury in MPVECs. Taken together, Dex treatment attenuated ischemia-reperfusion induced pulmonary injury through modulating the miR-21-5p/Nr4a1 signaling pathway.

Association between Socioeconomic Status and One-Month Mortality after Surgery in 20 Primary Solid Tumors: a Pan-Cancer Analysis.

Background: Surgery is the main therapy for primary solid tumors. One-month postoperative mortality remains an important criterion for assessing the quality of surgery. Socioeconomic status (SES) plays an important role in the biopsychosocial medical model. We performed a pan-cancer analysis to explore the relationship between SES and one-month mortality after surgery in 20 primary solid tumors. Methods: Eight SES factors and the top 20 common cancer sites were selected between 2007 and 2014 based on the Surveillance, Epidemiology, and End Results database. The primary outcome was that patients died within one month after surgery. The control group survived beyond one month. Multivariable logistic regression model, propensity score matching and subgroup analysis were used to detect the association. Results: There were 15980 (1.4%) patients who died within one month after surgery among 1132666 patients with primary solid cancers. Patients with unmarried status (aOR 1.516, 95% CI 1.462-1.573, P < 0.001), Medicaid/uninsured status (aOR 1.610, 95% CI 1.534-1.689, P < 0.001), low income (aOR 1.122, 95% CI 1.053-1.196, P < 0.001), low education (aOR 1.088, 95% CI 1.033-1.146, P = 0.001), or high poverty (aOR 1.085, 95% CI 1.026-1.147, P = 0.004) had high risks of one-month postoperative mortality. After propensity score matching and subgroup analysis, the effects of marriage and insurance on mortality were almost consistent with overall. Conclusions: There was a strong association between SES status and one-month postoperative mortality in primary solid tumors. Socioeconomically disadvantaged people had high risks of dying within one month after surgery. Unmarried or Medicaid/uninsured status were associated with much higher risks than other factors.

Levels of miR-125a-5p are altered in Mycobacterium avium-infected macrophages and associate with the triggering of an autophagic response.

Macrophages are major pathogen-killing cells. Mycobacteria can represent a serious threat to human health, in particular Mycobacterium tuberculosis and, less so, the opportunistic Mycobacterium avium. They can cause disseminated infections because of their capacity to survive and proliferate within macrophage phagolysosomes. Accumulating evidence indicates that the regulation of miRNA expression is implicated in the mechanisms of defense of macrophages against mycobacterial infections. Nevertheless, the precise contribution of miRNAs is largely unknown. The present study analyzes the expression profile of miRNAs during M. avium infection of macrophages by means of microarrays. We detected that the levels of 23 miRNAs were significantly changed ≥2.5-fold 24 h after M. avium infection. In particular, MiR-125a-5p was found to be highly expressed as part of the known immunological response of macrophages to bacterial or viral infections. MiR-125a-5p overexpression inhibited the expression of target signal transducers and activators of transcription 3 (STAT3) in THP-1 cells. Conversely, inhibitors of miR-125a-5p had the opposite effect. Silencing of STAT3 significantly enhanced the level of autophagy in both uninfected and M. avium-infected cells. Overexpression of miR-125a-5p significantly increased autophagy and decreased M. avium survival within THP-1 cells. Instead, co-transfection with miR-125a-5p mimic and a human STAT3 expressing construct reversed the effects: autophagy decreased and intracellular bactericidal survival was improved. Taken together, our findings indicate that miR-125a-5p participates in the regulation of innate host defenses by targeting STAT3 and enhancing autophagy levels. The results reported here contribute to a better understanding of host defense mechanisms against mycobacterial infections and offer some clues about their control.

Nomograms to predict survival of stage IV tongue squamous cell carcinoma after surgery.

To develop clinical nomograms for prediction of overall survival (OS) and cancer-specific survival (CSS) in patients with stage IV tongue squamous cell carcinoma (TSCC) after surgery based on the Surveillance, Epidemiology, and End Results (SEER) program database.We collected data of resected stage IV TSCC patients from the SEER database, and divided them into the training set and validation set by 7:3 randomly. Kaplan-Meier analysis and Cox regression analysis were adopted to distinguish independent risk factors for OS and CSS. Clinical nomograms were constructed to predict the 3-year and 5-year probabilities of OS and CSS for individual patients. Calibration curves and Harrell C-indices were used for internal and external validation.A total of 1550 patients with resected stage IV TSCC were identified. No statistical differences were detected between the training and validation sets. Age, race, marital status, tumor site, AJCC T/N/M status, and radiotherapy were recognized as independent prognostic factors associated with OS as well as CSS. Then nomograms were developed based on these variables. The calibration curves displayed a good agreement between the predicted and actual values of 3-year and 5-year probabilities for OS and CSS. The C-indices predicting OS were corrected as 0.705 in the training set, and 0.664 in the validation set. As for CSS, corrected C-indices were 0.708 in the training set and 0.663 in the validation set.The established nomograms in this study exhibited good accuracy and effectiveness to predict 3-year and 5-year probabilities of OS and CSS in resected stage IV TSCC patients. They are useful tools to evaluate survival outcomes and helped choose appropriate treatment strategies.

Impact of Insurance Status on Stage, Treatment, and Survival in Patients with Colorectal Cancer: A Population-Based Analysis.

BACKGROUND This study aimed to analyze data from the Surveillance, Epidemiology, and End Results (SEER) program to identify patients with colorectal cancer (CRC) who had specific insurance details and the effects of stage at diagnosis, definitive treatment, and survival outcome with insurance status. MATERIAL AND METHODS Between 2007 and 2009, SEER database analysis identified 54,232 patients with CRC. Logistic models examined the associations between insurance status and disease stage and definitive treatment. Kaplan-Meier analysis, the Cox model, and the Fine and Gray model were used to compare the tumor cause-specific survival (TCSS) for patients with different insurance status. RESULTS Insured patients were more likely to have earlier tumor stage at diagnosis when compared with patients receiving Medicaid (adjusted OR, 1.318; 95% CI, 1.249-1.391; P<0.001) and when compared with uninsured patients (adjusted OR, 1.479; 95% CI, 1.352-1.618; P<0.001). Insured patients were significantly more likely to undergo definitive treatment when compared with patients receiving Medicaid (adjusted OR, 0.591; 95% CI, 0.470-0.742; P<0.001) and compared with patients who were uninsured (adjusted OR, 0.404; 95% CI, 0.282-0.579; P<0.001). Insured patients had a significantly increased TCSS when compared with patients receiving Medicaid (HR, 1.298; 95% CI, 1.236-1.363; P<0.001) and compared with patients who were uninsured (HR 1.195, 95% CI, 1.100-1.297; P<0.001). CONCLUSIONS Insurance status was a significant factor that determined early diagnosis, definitive treatment, and clinical outcome and was an independent factor for TCSS in patients with CRC.

Nomogram Predicting Cause-Specific Mortality in Nonmetastatic Male Breast Cancer: A Competing Risk Analysis.

Introduction: Male breast cancer (MBC) is a rare tumor with few cases for research. Using the Surveillance, Epidemiology, and End Results program database, we carried out a competing risk analysis in patients with primary nonmetastatic MBC and built a predictive nomogram. Materials and Methods: We extracted primary nonmetastatic MBC patients according to the inclusion and exclusion criteria. Cumulative incidence function (CIF) and proportional subdistribution hazard model were adopted to explore risk factors for breast cancer-specific death (BCSD) and other cause-specific death (OCSD). Then we built a nomogram to predict the 3-year, 5-year and 8-year probabilities of BCSD and OCSD. C-indexes, Brier scores and calibration curves were chosen for validation. Results: We identified 1,978 nonmetastatic MBC patients finally. CIF analysis showed that the 3-year, 5-year and 8-year mortalities were 5.2%, 10.6% and 16.5% for BCSD, and 6.1%, 9.6% and 14.4% for OCSD. After adjustment of Fine and Gray models, black race, PR (-), advanced T/N/grade and no surgery were independently associated with BCSD. Meanwhile, elderly, unmarried status, advanced AJCC stage and no chemotherapy resulted in OCSD more possibly. A graphic nomogram was developed according to the coefficients from the Fine and Gray models. The calibration curves displayed exceptionally, with C-indexes nearly larger than 0.700 and Brier scores nearly smaller than 0.100. Conclusion: The competing risk nomogram showed good accuracy for predictive prognosis in nonmetastatic MBC patients. It was a useful implement to evaluate crude mortalities of BCSD and OCSD, and help clinicians to choose appropriate therapeutic plans.

MicroRNA­214 suppresses propofol­induced neuroapoptosis through activation of phosphoinositide 3­kinase/protein kinase B signaling by targeting phosphatase and tensin homolog expression.

The present study aimed to investigate the effects of microRNA (miR)­214 on neuroapoptosis induced by propofol and the possible mechanism of its anti­apoptotic effects. Initially, it was observed that miR­214 expression was upregulated in propofol­induced neuroapoptosis rats. Next, propofol­treated nerve cells were transfected with miR­214 mimics. The results revealed that miR­214 overexpression induced apoptosis, inhibited cell proliferation, inhibited cyclin D1 protein expression, promoted caspase­3 activity and B­cell lymphoma 2­associated X protein expression, and enhanced the levels of inflammation factors in nerve cells treated with propofol. In addition, miR­214 overexpression suppressed phosphoinositide 3­kinase/protein kinase B (PI3K/Akt) signaling by targeting the activation of phosphatase and tensin homolog (PTEN) and nuclear factor­κB expression in nerve cells treated with propofol. Treatment with a PTEN inhibitor successfully suppressed the PTEN protein expression and decreased the apoptosis of propofol­treated nerve cells subsequent to miR­214 overexpression through PI3K/Akt signaling. In conclusion, the present study data revealed that miR­214 suppressed propofol­induced neuroapoptosis through the activation of PI3K/Akt signaling by targeting PTEN expression.

Matrine inhibits IL-1ß-induced expression of matrix metalloproteinases by suppressing the activation of MAPK and NF-κB in human chondrocytes in vitro.

Interleukin (IL)-1ß plays an important role in promoting osteoarthritis (OA) lesions by inducing chondrocytes to secrete matrix metalloproteinases (MMPs), which degrade the extracellular matrix and facilitate chondrocyte apoptosis. Matrine was shown to exert anti-inflammatory effects. However, the role of matrine in OA is still unclear. Therefore, in this study, we investigated the effects of matrine on the expression of MMPs in IL-1ß-treated human chondrocytes and the underlying mechanism. The cell viability of chondrocytes was detected by MTT assay. The cell apoptosis of chondrocytes was measured by flow cytometric analysis. The protein production of MMPs was determined by ELISA. The protein expression of phosphorylation of mitogen-activated protein kinases (MAPKs) and the inhibitor of kappaB alpha (IκBα) was determined by Western blot. Matrine significantly inhibited the IL-1ß-induced apoptosis in chondrocytes. It also significantly inhibited the IL-1ß-induced release of MMP-3 and MMP-13, and increased the production of TIMP-1. Furthermore, matrine inhibits the phosphorylation of p-38, extracellular regulated kinase (ERK), c-Jun-N-terminal kinase (JNK) and IκBα degradation induced by IL-1ß in chondrocytes. Taken together, our results show that matrine inhibits IL-1ß-induced expression of matrix metalloproteinases by suppressing the activation of MAPK and NF-κB in human chondrocytes in vitro. Therefore,-matrine may be beneficial in the treatment of OA.

Nuclear factor-kappa B mediates one-lung ventilation-induced acute lung injury in rabbits.

INTRODUCTION: Several studies have revealed the adverse effect of one-lung ventilation (OLV) on pulmonary function. Nuclear factor-kappa B (NF-κB) is a principal transcription factor of proinflammatory genes. This study was designed to investigate the role of NF-κB in OLV-mediated lung injury. METHODS: Male rabbits, weighing 2.2 ± 0.3 kg, were randomly divided into five groups: sham tracheostomized (Sham), OLV (V(T) = 10 ml/kg, FiO(2) = 1.0), two-lung ventilation (TLV, V(T) = 10 ml/kg, FiO(2) = 1.0), OLV preceded by the treatment with NF-κB inhibitor pyrrolidine dithiocarbamate (PDTC, 50 mg/kg, i.v.), and TLV with the PDTC pretreatment. Arterial blood gases, lung pathological changes, and production of proinflammatory cytokines (tumor necrosis factor-α and interleukin-8) were assessed. NF-κB activation was determined by electrophoretic mobility shift assay (EMSA) and western blotting of nuclear NF-κB p65. RESULTS: The OLV significantly decreased the ratio of partial pressure of oxygen and fraction inspired oxygen (PaO(2)/FiO(2)) compared to the Sham group (p < .01). However, the TLV had no evident effect on the PaO(2)/FiO(2) ratio. The pretreatment with PDTC significantly reversed the OLV-induced reduction in the PaO(2)/FiO(2) ratio. The PDTC pretreatment also markedly attenuated the OLV-mediated lung injury and proinflammatory cytokine production. The OLV potentiated the NF-κB DNA binding activity assessed by EMSA and the NF-κB nuclear translocation. The OLV-mediated NF-κB activation was markedly inhibited by the PDTC pretreatment. CONCLUSION: Our data collectively demonstrate that OLV can cause lung injury through the activation of NF-κB and the production of proinflammatory cytokines. Blocking NF-κB reduces lung inflammation and may be an effective strategy in the management of OLV-induced lung damage.

Bosentan affects 15-F2t-isoprostane adverse effects on postischemic rat hearts.

BACKGROUND: 15-F(2t)-isoprostane (IsoP), a marker of reactive oxygen species-induced oxidative stress, is increased after myocardial ischemia and reperfusion. It exerts deleterious effects on postischemic myocardium accompanied with increased release of endothelin-1 (ET-1), a potent vasoconstrictor. We hypothesized that IsoP exacerbates myocardial ischemia-reperfusion injury by stimulating ET-1 production, and that ET-1 blockade can attenuate or prevent these deleterious effects of IsoP. METHODS: Adult rat hearts were perfused by the Langendorff technique with Krebs-Henseleit solution (KH) at a constant flow rate of 10 mL/min. Global myocardial ischemia was induced by stopping KH perfusion for 40 min followed by 60 min of reperfusion. Hearts were randomized to one of the five groups (n = 8 each): untreated control, treated with IsoP (100 nM), or the ET-1 receptor A/B antagonist bosentan (1 µM) alone or in combination 10 min prior to, during 40 min global ischemia and 15 min of reperfusion, or treated with IsoP as above plus delayed administration of bosentan after 15 min of reperfusion. RESULTS: Coronary effluent ET-1 concentrations in the IsoP group were higher than those in the control group during ischemia and reperfusion (P < 0.05), which was associated with increased release of cardiac-specific creatine kinase, reduced cardiac contractility during reperfusion, and increased myocardial infarct size (all P < 0.05 versus control). Bosentan administration during early reperfusion exacerbated the IsoP deleterious effects, while delayed administration attenuated it. CONCLUSION: 15-F(2t)-isoprostane-induced ET-1 production during later reperfusion is detrimental to functional recovery of damaged myocardium, while ET-1 increase during early reperfusion seems to improve it.

[Effect of tryptase inhibitors on histamine release from human colon mast cells].

AIM: To investigate the effect of tryptase inhibitors (TPIs) on histamine release from human colon mast cells. METHODS: Human mast cells were prepared by digestion of colon tissue and with collagenase and hyaluronidase, cultured with four kinds of TPIs, leupeptin, protamine, TLCK, and lactoferrin for 15 min at 37 degrees Celsius respectively. A glass fibre-based fluorometry assay was used to detect histamine in mast cell suspension. RESULTS: 200 mmol/L leupeptin and 100 mmol/L protamine were able to stimulate histamine release from colon mast cells, while TLCK and lactoferrin did not. All TPIs inhibited anti-IgE-induced histamine release in a concentration dependent manner, and the inhibitory rates were 48.7%, 36.7%, 40.2% and 34.1%, respectively. However preincubation of TPIs with mast cells for 20 min at 37 degrees Celsius before adding anti-IgE had little effect on anti-IgE induced histamine release. All TPIs were able to inhibit calcium ionophore (CI)-induced histamine release, and the maximum inhibition rate was between 25%-32%. Inhibition on histamine release by leupeptin and TLCK obviously enhanced when colon mast cells were preincubated with them for 20 min before adding CI. However, under the same condition, protamine failed to inhibit histamine release. CONCLUSION: We prove for the first time that TPIs inhibit anti-IgE-and CI-induced histamine release from human colon mast cells, suggesting that it is possible to treat inflammatory bowel disease or other mast cell-related diseases by using TPIs.

[Effects of extracellular signal-regulated kinase inhibition by AG126 on tissue tumor necrosis factor-alpha expression and multiple organ dysfunction in rats with postburn Staphylococcus aureus sepsis].

OBJECTIVE: To investigate the effects of extracellular signal-regulated kinase (ERKs) inhibition by AG126 on tissue tumor necrosis factor-alpha (TNF-alpha) expression and multiple organ dysfunction in rats with postburn Staphylococcus aureus sepsis and its potential signal regulating mechanism. METHODS: To reproduce postburn sepsis model, male Wistar rats were inflicated with 20% total body surface area third-degree scald followed by Staphylococcus aureus challenge. 34 rats were randomly divided into four groups as follows: normal control group (n = 6), scald control group (n = 6), postburn sepsis group (n = 12), and AG126 treatment group (n = 10). Tissue samples from the liver, kidneys and lungs were collected to determine phosphorylated ERKs by Western blot analysis, and TNF-alpha mRNA expression as well as its protein levels. RESULTS: It was revealed that phosphorylated ERKs in the liver, lungs, and kidneys from postburn septic animals were up-regulated rapidly at 0.5 - 2.0 hours, being 1.94-fold (P < 0.05), 2.86-fold (P < 0.01), and 1.41-fold at 2.0 hours compared to normal controls, respectively. Treatment with AG126 could significantly reduce phosphorylated ERKs in lung tissue by 70.6% (P < 0.01) at 2.0 hours postburn sepsis, and almost completely inhibited ERKs activation in the liver and kidneys at various time points. Meanwhile, both TNF-alpha mRNA and protein expressions in the liver, lungs, and kidneys were significantly decreased in AG126-treated group following septic challenge (P < 0.05 or 0.01). In addition, 2.0 hours after Staphylococcus aureus infection, treatment with AG126 markedly improved hepatic and renal function parameters, including serum ALT, AST, Cr, as well as BUN levels (P < 0.05 or 0.01), together with significant decrease in pulmonary myeloperoxidase activity, compared to those without AG126 treatment. CONCLUSION: These data suggested that ERKs signal transduction might be involved in the pathogenesis of systemic inflammatory response and multiple organ dysfunction in postburn gram-positive bacterial sepsis. Early treatment with AG126 could significantly down-regulate TNF-alpha mRNA expression as well as protein levels in vital organs and attenuate multiple organ dysfunction induced by scald injury combined with Staphylococcus aureus challenge.

[Changes in Toll-like receptor 2 and 4 gene expression in vital organs in septic rats and their regulation mechanisms].

OBJECTIVE: To investigate the changes in Toll-like receptor (TLR) 2 and 4 gene expression in vital organs in septic rats and their potential regulation mechanism. METHODS: One hundred Wistar rats were randomly divided into normal controls (n=10), sham-operated group (n=10), septic group (n=60), and recombinant bactericidal/permeability increasing protein (BPI)-treated group (n=20). Severe sepsis was replicated by cecal ligation and puncture (CLP). Animals were sacrificed at different time points after CLP, tissue TLR2/4 mRNA expression in the liver, lungs, kidneys as well as intestine were measured by reverse transcription-polymerase chain reaction (RT-PCR). Plasma levels of tumor necrosis factor-alpha(TNF-alpha) and interleukin-10 (IL-10) were also determined by enzyme linked immunoadsorbent assay (ELISA). RESULTS: TLR2/4 mRNA could be detected in various tissues with low values both in normal controls and sham-operated group, but they were markedly up-regulated at 2 hours after CLP, peaking at 6-12 hours. Tissue TLR4 mRNA was gradually down-regulated 24 hours later, while TLR2 mRNA levels maintained high values up to 72 hours. In comparison with the CLP group, treatment with BPI significantly decreased TLR2 mRNA in various tissues at 12 and 24 hours (P<0.05 or P<0.01), also tissue TLR4 mRNA at 12 hours (P<0.05 or P<0.01), without marked influence on TLR4 mRNA expression at 24 hours in liver, lungs and small intestine (P>0.05). In addition, treatment with BPI could significantly lower plasma TNF-alpha levels at 12 hours post-CLP, on the other hand markedly elevate plasma IL -10 levels 24 hours later (P<0.01). CONCLUSION: These data suggest that severe peritoneal infection could result in up-regulation of TLR2/4 mRNA expression in vital organs, which might play important roles in mediating proinflammatory cytokine synthesis and release. Endotoxemia appears to be involved in the activation of tissue TLR2/4 expression associated with CLP-induced sepsis.

[Effects of esmolol and fentanyl on the hemodynamic and catecholamine response to tracheal intubation in hypertensive patients].

OBJECTIVE: To compare effects of esmolol and fentanyl on the hemodynamic and catecholamine response to tracheal intubation in hypertensive patients. METHODS: Sixty hypertensive patients were randomly allocated into one of four groups: the patients received 0.9% saline in group A, 2 mg/kg esmolol in group B, 2 microg/kg fentanyl in group C and 2 mg/kg esmolol combined with 2 microg/kg fentanyl in group D before intubation. Tracheal intubation was performed with 0.1 mg/kg midazolam, 0.6 mg/kg atracurium and 2 mg/kg propofol. Systolic arterial pressure (SAP), diastolic arterial pressure (DAP), heart rate (HR), rate-pressure product (RPP), plasma noradrenaline (NA) and adrenaline (A) concentrations were measured before and after intubation. RESULTS: SAP, DAP, HR, RPP, NA and A levels in group A at 1 and 3 minutes after intubation were significantly higher than the baseline values (all P<0.01). NA levels in group B and SAP in group C increased significantly after intubation (both P<0.05). The hemodynamics and catecholamine in group D after intubation were not significantly different from the baselines (all P>0.05). CONCLUSION: 2 mg/kg esmolol or 2 microg/kg fentanyl can partly reduce hemodynamic response to intubation and 2 mg/kg esmolol combined with 2 microg/kg fentanyl can completely attenuate the hemodynamic and catecholamine response in hypertensive patients.