MetEx: A Targeted Extraction Strategy for Improving the Coverage and Accuracy of Metabolite Annotation in Liquid Chromatography-High-Resolution Mass Spectrometry Data.

Liquid chromatography-high-resolution mass spectrometry (LC-HRMS) is the most popular platform for untargeted metabolomics studies, but compound annotation is a challenge. In this work, we developed a new LC-HRMS data-targeted extraction method called MetEx for metabolite annotation. MetEx contains the retention time (tR), MS1, and MS2 information of 30 620 metabolites from freely available spectral databases, including MoNA and KEGG. The tR values of 95.4% of the compounds in our database were calculated by the GNN-RT model. The MS2 spectra of 39.4% compounds were also predicted using CFM-ID. MetEx was initially examined on a mixture of 634 standards, considering chemical coverage and accurate metabolite assignment, and later applied to human plasma (NIST SRM 1950), human urine, HepG2 cells, mouse liver tissue, and mouse feces. MetEx correctly assigned 252 out of 253 standards detected in our instruments. The platform also provided 8.0-44.2% more compounds in the biological samples compared to XCMS, MS-DIAL, and MZmine 2. MetEx is implemented and visualized in R and freely available at http://www.metaboex.cn/MetEx.

The inhibition of circular RNA circNOLC1 by propofol/STAT3 attenuates breast cancer stem cells function via miR-365a-3p/STAT3 signaling.

BACKGROUND: Breast cancer remains one of the most dreadful female malignancies globally, in which cancer stem cells (CSCs) play crucial functions. Circular RNAs have drawn great attention in cancer research area and propofol is a widely applied intravenous anesthetic agent. METHODS: In the current study, we explored the function of circular RNA nucleolar and coiled-body phosphoprotein 1 (circNOLC1) in CSCs of breast cancer and the inhibitory impact of propofol on circNOLC1. RESULTS: The expression of circNOLC1 was induced in breast cancer tissues compared with the non-tumor tissues. The silencing of circNOLC1 was able to repress the viability of breast cancer cells. Meanwhile, the numbers of colony formation were suppressed by circNOLC1 knockdown in breast cancer cells. The inhibition of circNOLC1 reduced the invasion and migration ability of breast cancer cells. The mRNA and protein levels of E-cadherin were enhanced but Vimentin levels were reduced by the silencing of circNOLC1. The repression of circNOLC1 decreased the side population (SP) ratio in breast cancer cells. Meanwhile, the sphere formation ability of breast cancer cells was attenuated by the silencing of circNOLC1. The levels of ATP-binding cassette (ABC) superfamily G member 2 (ABCG2), c-Myc, B cell-specific Moloney murine leukemia virus integration site 1 (Bmi1), and SRY-box transcription factor 2 (Sox2) were repressed by the depletion of circNOLC1 in the cells. Regarding to the mechanism, circNOLC1 functioned as a competing endogenous RNAs (ceRNAs) for microRNA-365a-3p (miR-365a-3p) and the inhibition of miR-365a-3p rescued circNOLC1 depletion-repressed proliferation and cancer stem cell activity of breast cancer. MiR-365a-3p targeted signal transducer and activator of transcription 3 (STAT3) in breast cancer cells and circNOLC1 enhanced STAT3 expression by sponging miR-365a-3p. The overexpression of STAT3 could reverse miR-365a-3p or circNOLC1 depletion-inhibited proliferation and cancer stem cell properties of breast cancer. Interestingly, the expression of circNOLC1 and STAT3 was repressed by the treatment of propofol. The enrichment of STAT3 on circNOLC1 promoter was inhibited by propofol. The expression of circNOLC1 was suppressed by the silencing of STAT3 in the cells. The inhibition of circNOLC1 expression by propofol was rescued under the co-treatment of STAT3 overexpression. The overexpression of circNOLC1 rescued propofol-attenuated proliferation and cancer stem cell functions in vitro and in vivo. CONCLUSIONS: Thus, we concluded that circNOLC1 contributes to CSCs properties and progression of breast cancer by targeting miR-365a-3p /STAT3 axis and propofol inhibited circNOLC1 by repressing STAT3 in a feedback mechanism.

Volatile Organic Compounds to Identify Infectious (Bacteria/Viruses) Diseases of the Central Nervous System: A Pilot Study.

BACKGROUND: Central nervous system (CNS) infectious diseases are common diseases in emergency rooms and neurology departments. CNS pathogen identification methods are time consuming and expensive and have low sensitivity and poor specificity. Some studies have shown that bacteria and viruses can produce specific volatile organic compounds (VOCs). The aim of this study is to find potential biomarkers by VOC analysis of cerebrospinal fluid (CSF) in patients with bacterial and viral meningitis/encephalitis (ME). METHODS: CSF samples from 16 patients with bacterial ME and 42 patients with viral ME were collected, and solid-phase microextraction combined with gas chromatography-mass spectrometry was used to analyze the metabolites in the CSF. RESULTS: There are 2 substances (ethylene oxide and phenol) that were found to be different between the 2 groups. Ethylene oxide was significantly greater in the group of bacterial ME patients than in the viral ME group of patients (p < 0.05). In addition, phenol was remarkably increased in the group of ME patients compared with the bacterial ME patients (p < 0.05). CONCLUSIONS: Ethylene oxide and phenol may be potential biomarkers to distinguish bacterial ME and viral ME. VOC analysis of CSF may be used as a supporting tool for clinical diagnosis.

Liquid Chromatography-Mass Spectrometry-Based Tissue Metabolic Profiling Reveals Major Metabolic Pathway Alterations and Potential Biomarkers of Lung Cancer.

Unclarified molecular mechanism and lack of practical diagnosis biomarkers hinder the effective treatment of non-small-cell lung cancer. Herein, we performed liquid chromatography-mass spectrometry-based nontargeted metabolomics analysis in 131 patients with their lung tissue pairs to study the metabolic characteristics and disordered metabolic pathways in lung tumor. A total of 339 metabolites were identified in metabolic profiling. Also, 241 differential metabolites were found between lung carcinoma tissues (LCTs) and paired distal noncancerous tissues; amino acids, purine metabolites, fatty acids, phospholipids, and most of lysophospholipids significantly increased in LCTs, while 3-phosphoglyceric acid, phosphoenolpyruvate, 6-phosphogluconate, and citrate decreased. Additionally, pathway enrichment analysis revealed that energy, purine, amino acid, lipid, and glutathione metabolism are markedly disturbed in lung cancer (LCa). Using binary logistic regression, we further defined candidate biomarkers for different subtypes of lung tumor. Xanthine and PC 35:2 were selected as combinational biomarkers for distinguishing benign from malignant lung tumors with a 0.886 area under curve (AUC) value, and creatine, myoinositol and LPE 16:0 were defined as combinational biomarkers for discriminating adenocarcinoma from squamous cell lung carcinoma with a 0.934 AUC value. Overall, metabolic characterization and pathway disturbance demonstrated apparent metabolic reprogramming in LCa. The defined candidate metabolite marker panels are useful for subtyping of lung tumors to assist clinical diagnosis.

Dexmedetomidine reduces the inflammation and apoptosis of doxorubicin-induced myocardial cells.

As the number of elderly patients increases, some patients with heart problems may also need surgery. The purpose of this study was to investigate whether dexmedetomidine (DEX), a common used anesthetic, was beneficial to the patients with heart problems. Myocardial cells induced by doxorubicin (DOX) was to simulate the myocardium injury in vitro. H9c2 cells were treated with DOX, DEX/DOX, Compound C and Compound C/DEX/DOX, respectively. The expression of p-AMPK, AMPK, p-GSK3ß, GSK3ß, Bcl2, Bax, Cleaved caspase3, Caspase3, TXNIP, NLRP3, ASC, Cleaved caspase-1 and Caspase-1 were analyzed by Western blot. CCK-8 assay and flow cytometry analysis were used to detect the cell viability and cell apoptosis. The levels of TNF-α, IL-1ß and IL-18 were detected by ELISA assay and the levels of NO, ROS, LDH, SOD, MDA and taurine were detected by corresponding assay kits. As a result, DEX promoted the cell viability and inhibited the inflammation, oxidative stress and apoptosis. In addition, DEX suppressed the expression of taurine, TXNIP, NLRP3, ASC and cleaved caspase-1 and activated the expression of p-AMPK and p-GSK3ß. However, those above changes could be reversed by Compound C. In conclusion, this study indicated that DEX could reduce the inflammation and apoptosis of DOX-induced myocardial cells through activating the AMPK-GSK3ß signaling pathway. Because of the above effects of DEX, it may be beneficial for surgical patients with heart problems.

Early diagnosis of breast cancer from exhaled breath by gas chromatography-mass spectrometry (GC/MS) analysis: A prospective cohort study.

BACKGROUND: It has proved that there is an association between cancer and volatile organic compounds (VOCs) of exhaled breath. This study targets on verifying the existence of specific VOCs in breathing in breast cancer patients, especially those with ductal carcinoma in situ (DCIS). METHODS: There were a total of 203 participants included in the final analysis, which included 71 (35.0%) patients with histologically confirmed breast cancer (including 13 with DCIS, 31 with lymph node metastasis-negative status, and 27 with lymph node metastasis-positive status), 78 (38.4%) healthy volunteers, and 54 (26.6%) patients with histologically confirmed gastric cancer. Gas chromatography-mass spectrometry and solid-phase microextraction were used to analyze the breath samples for the presence of VOCs. RESULTS: There were significant differences in the volatile organic metabolites between the DCIS, lymph node metastasis-negative breast cancer, and lymph node metastasis-positive breast cancer groups compared with the healthy controls as well as between the breast cancer and gastric cancer patients. An overlapping set of seven VOCs, including (S)-1,2-propanediol, cyclopentanone, ethylene carbonate, 3-methoxy-1,2-propanediol, 3-methylpyridine, phenol, and tetramethylsilane, was significantly different between the breast cancer patients and healthy individuals as well as between the breast cancer and gastric cancer patients. The combination of these seven compounds was considered as a biomarker for breast cancer. The sensitivity for predicting DCIS by this set of seven compounds was determined to be 80.77%, and the specificity was determined to be 100%. CONCLUSIONS: This set of seven breast cancer-specific VOCs can be regarded as one particular expiratory marker for DCIS and will help to establish new screening methods for early breast cancer.

Online Monitoring of Intraoperative Exhaled Propofol by Acetone-Assisted Negative Photoionization Ion Mobility Spectrometry Coupled with Time-Resolved Purge Introduction.

Online monitoring of exhaled propofol concentration is important for anesthetists to provide adequate anesthesia as propofol concentrations in plasma and breath are correlated reasonably well. Exhaled propofol could be detected by 63Ni ion mobility spectrometry in negative ion mode; however, the radioactivity of 63Ni source restricts its clinical application due to safety, environmental, and regulatory concerns. An acetone-assisted negative photoionization ion mobility spectrometer (AANP-IMS) using a side-mounted vacuum ultraviolet (VUV) lamp in the unidirectional (UD) flow mode was developed for sensitive measurement of exhaled propofol by producing a high percentage of O2-(H2O) n. An adsorption sampling and time-resolved purge introduction system was developed to eliminate the interference of residual inhaled anesthetic sevoflurane based on their different adsorptions between propofol and sevoflurane on the inwall of the fluorinated ethylene propylene (FEP) sample loop. The effects of the inner diameter and the length of the sample loop on the signal intensity of propofol and the time-resolution between propofol and sevoflurane were theoretically and experimentally investigated. A sample loop with 3 mm i.d. and 150 cm length allowed sensitive measurement of exhaled propofol with a response time of 4 s, a linear response range for propofol was achieved to be 0.2 to 14 ppbv with a limit of detection (LOD) of 60 pptv, and the quantification of propofol was not influenced by the change of the sevoflurane concentration. Finally, the performance of monitoring exhaled propofol during surgery was demonstrated on a patient undergoing laparoscopic distal pancreatectomy combined with cholecystectomy.

Urine volatile organic compounds as biomarkers for minimal change type nephrotic syndrome.

Urinary volatile organic compounds (VOCs) profiling has recently received considerable attention because it can be obtained noninvasively and conveniently while it can be successfully used in a variety of diseases and can provide unique biomarkers. The aim of current study was to investigate potential biomarkers between minimal change type nephrotic syndrome (MCNS) and normal. Urinary samples were collected from 38 minimal change type nephrotic syndrome patients and 15 healthy controls. Solid phase microextraction (SPME) and chromatography- mass spectrometry (GC-MS) were used to analysis the urinary metabolites. To deal with the final data, the statistical methods principal component analysis (PCA) and orthogonal partial least-squares discriminant analysis (OPLSDA) were performed. Six specific VOC biomarkers were present at abnormal levels in the urine of MCNS patients. These VOCs included trans-2,2-dimethyl-4-decene; pyrrole; carbamic acid, monoammonium salt; 1-butyne, 3,3-dimethyl-; diisopropylamine; and 4-heptanone. These biomarkers may be useful as a new diagnostic method and for monitoring the prognosis for MCNS patients.

Volatile organic metabolites identify patients with gastric carcinoma, gastric ulcer, or gastritis and control patients.

BACKGROUND: Gastric cancer ranks 4th among the most common cancers worldwide, and the mortality caused by gastric cancer is 2nd only to lung cancer. Gastric cancer shows a lack of specific symptoms in its early stages. In addition, its clinical symptoms often do not match the corresponding stage. Upper gastrointestinal endoscopy with biopsy is the gold standard for the diagnosis of gastric cancer because of its high accuracy. However, this operation is invasive, patient compliance is poor, and high demands for medical staff and equipment are typical of this procedure. Recent studies have demonstrated a connection between specific breath volatile organic compounds (VOCs) and various forms of cancers. METHODS: We collected expired air from patients with gastric cancer, chronic atrophic gastritis or gastric ulcers as well as from healthy individuals. Solid-phase microextraction, gas chromatography-mass spectrometry and principal component analysis statistics were applied to identify potential biomarkers of gastric cancer among VOCs. RESULTS: Fourteen differential metabolites were annotated using the NIST 11 database, with a similarity threshold of 70%. Currently, the metabolic origin of VOCs remains unclear; however, several pathways might explain the decreasing or increasing trends that were observed. CONCLUSIONS: The results of this study demonstrate the existence of specific VOC profiles associated with patients with carcinoma. In addition, these metabolites may contribute to the diagnosis and screening of patients with carcinoma.

Effects of Propofol on Several Membrane Characteristics of Cervical Cancer Cell Lines.

BACKGROUND: Although significant advances have been made toward understanding the molecular mechanisms underlying the effect of propofol on tumor cell metastasis, less is known regarding how cell membrane and cytoskeletal ultrastructure are affected in this process. Here, we investigated the relationship between cell morphology and cell size, which are features mainly defined by the cytoskeleton. METHODS: To confirm the effects of propofol on the migratory ability of human cervical carcinoma cells, cell migration and invasion were examined through scratch wound healing and transwell membrane assays. Furthermore, HeLa cells cultivated with different concentrations of propofol were examined by confocal microscopy and atomic force microscopy (AFM), and the mean optical density and migration ability of these cells were also assessed. In addition, cell membrane morphology was inspected using AFM. RESULTS: The results of the wound healing and transwell membrane assays indicated that propofol decreases the migratory ability of cervical carcinoma cells compared to control cells. A comparative analysis of the test results revealed that short-term (3 h) exposure to propofol induced marked changes in cell membrane microstructure and in the cytoskeleton in a dose-dependent manner. These morphological changes in the cell membrane were accompanied by cytoskeleton (F-actin) derangement. The present findings demonstrate a close relationship between changes in cell membrane ultrastructure and cytoskeletal alterations (F-actin) in propofol-treated HeLa cells. AFM scanning analysis showed that cell membrane ultrastructure was significantly changed, including a clear reduction in membrane roughness. CONCLUSION: The influence of propofol on the HeLa cell cytoskeleton can be directly reflected by changes in cellular morphology, as assessed by AFM. Moreover, the use of AFM is a good method for investigating propofol-mediated changes within cytoskeletal ultrastructure.

Mechanical ventilation strategies for intensive care unit patients without acute lung injury or acute respiratory distress syndrome: a systematic review and network meta-analysis.

BACKGROUND: It has been shown that the application of a lung-protective mechanical ventilation strategy can improve the prognosis of patients with acute lung injury (ALI) or acute respiratory distress syndrome (ARDS). However, the optimal mechanical ventilation strategy for intensive care unit (ICU) patients without ALI or ARDS is uncertain. Therefore, we performed a network meta-analysis to identify the optimal mechanical ventilation strategy for these patients. METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) in the Cochrane Library, EMBASE, MEDLINE, CINAHL, and Web of Science for studies published up to July 2015 in which pulmonary compliance or the partial pressure of arterial oxygen/fraction of inspired oxygen (PaO2/FIO2) ratio was assessed in ICU patients without ALI or ARDS, who received mechanical ventilation via different strategies. The data for study characteristics, methods, and outcomes were extracted. We assessed the studies for eligibility, extracted the data, pooled the data, and used a Bayesian fixed-effects model to combine direct comparisons with indirect evidence. RESULTS: Seventeen randomized controlled trials including a total of 575 patients who received one of six ventilation strategies were included for network meta-analysis. Among ICU patients without ALI or ARDS, strategy C (lower tidal volume (VT) + higher positive end-expiratory pressure (PEEP)) resulted in the highest PaO2/FIO2 ratio; strategy B (higher VT + lower PEEP) was associated with the highest pulmonary compliance; strategy A (lower VT + lower PEEP) was associated with a shorter length of ICU stay; and strategy D (lower VT + zero end-expiratory pressure (ZEEP)) was associated with the lowest PaO2/FiO2 ratio and pulmonary compliance. CONCLUSIONS: For ICU patients without ALI or ARDS, strategy C (lower VT + higher PEEP) was associated with the highest PaO2/FiO2 ratio. Strategy B (higher VT + lower PEEP) was superior to the other strategies in improving pulmonary compliance. Strategy A (lower VT + lower PEEP) was associated with a shorter length of ICU stay, whereas strategy D (lower VT + ZEEP) was associated with the lowest PaO2/FiO2 ratio and pulmonary compliance.

Metabolomic analysis of serum from obese adults with hyperlipemia by UHPLC-Q-TOF MS/MS.

The prevalence of obesity has dramatically increased and poses a major threat to human health. Obesity often accompanies hyperlipemia, which is strongly related to the occurrence and development of obesity-related chronic diseases. Differences in metabolomic profiling of serum between obese (with hyperlipemia) and normal-weight men (n = 30 in each group) were investigated using ultrahigh-pressure liquid chromatography-quadrupole-time of flight mass spectrometry (UHPLC-Q-TOF MS/MS) and partial least-squares-discriminant analysis (PLS-DA). Obese men showed higher levels of weight, body mass index, fat mass, systolic blood pressure, fasting plasma glucose, triglyeride, total cholesterol, insulin, HOMA-IR and high-sensitivity CRP. Obese and normal-weight groups were clearly discriminated from each other on a PLS-DA score plot and nine major metabolites contributing to the discrimination were assigned, including increased 2-octenoylcarnitine, eicosadienoic acid, 12-hydroperoxyeicosatetraenoic acid, 4-hydroxyestrone sulfate, lysoPE[18:1(11Z)/0:0], thromboxane B2 and pyridinoline and decreased vitamin D3 glucosiduronate and 9,10-DHOME. These metabolites were associated with lipid metabolism and obesity-related diseases, and reflected the metabolic differences between normal and obese men, which may be important for future clinical diagnosis, treatment and assessment of the therapeutic effect on obesity-related chronic disease.

Mechanical ventilation modes for respiratory distress syndrome in infants: a systematic review and network meta-analysis.

INTRODUCTION: The effects of different mechanical ventilation (MV) modes on mortality outcome in infants with respiratory distress syndrome (RDS) are not well known. METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) in the Cochrane Library, EMBASE, MEDLINE, CINAHL, and Web of Science for studies published through April 2014 that assessed mortality in infants with RDS given different MV modes. We assessed studies for eligibility, extracted data, and subsequently pooled the data. A Bayesian fixed-effects model was used to combine direct comparisons with indirect evidence. We also performed sensitivity analyses and rankings of the competing treatment modes. RESULTS: In total, 20 randomized controlled trials were included for the network meta-analysis, which consisted of 2,832 patients who received one of 16 ventilation modes. Compared with synchronized intermittent mandatory ventilation (SIMV) + pressure support ventilation (PSV), time-cycled pressure-limited ventilation (TCPL) (hazard ratio (HR) 0.290; 95% confidence interval (CI) 0.071 to 0.972), high-frequency oscillatory ventilation (HFOV) (HR 0.294; 95% CI 0.080 to 0.852), SIMV + volume-guarantee (VG) (HR 0.122; 95% CI 0.014 to 0.858), and volume-controlled (V-C) (HR 0.139; 95% CI 0.024 to 0.677) ventilation modes are associated with lower mortality. The combined results of available ventilation modes were not significantly different in regard to the incidences of patent ductus arteriosus and intraventricular hemorrhage. CONCLUSION: Compared with the SIMV + PSV ventilation mode, the TCPL, HFOV, SIMV + VG, and V-C ventilation modes are associated with lower mortality.

Blockade of PDE4B limits lung vascular permeability and lung inflammation in LPS-induced acute lung injury.

Acute lung injury (ALI), acute respiratory distress syndrome (ARDS), is actually involved in an ongoing and uncontrolled inflammatory response in lung tissues. Although extensive studies suggested that phospodiesterase type 4B (PDE4B) may be related to inflammation, the underlying cell biological mechanism of ALI remains unclear. To further investigate the mechanism how PDE4B take part in inflammatory response and the maintenance of vascular integrity, we established the experimental model of ALI in vitro and in vivo. In vitro, we found that Cilomilast, Diazepam and PDE4B knockout could potently inhibit the LPS-induced NF-κB activation and inflammatory response in multiple cell types, including lung epithelial cells (A549), pulmonary microvascular endothelial cells (PMVECs) and vascular smooth muscle cells (VSMCs). Besides, PDE4B deletion attenuated the LPS-induced ROS generation. In vivo, PDE4B deletion could attenuate the lung water content, histological signs of pulmonary injury and elevate the ratio of partial pressure of arterial O2 to fraction of inspired O2 (PaO2/FIO2 ratio). Additionally, PDE4B deletion reduced LPS-induced vascular permeability. Collectively, our results strongly indicates that PDE4B is a valid target for anti-ALI.

Noninvasive detection of colorectal cancer by analysis of exhaled breath.

There has been growing interest in exhaled breath analysis for cancer screening and disease monitoring; however, limited breath biomarker information exists regarding colorectal cancer (CRC). The objective of this study was to screen for breath biomarkers of CRC. Exhaled breath was collected from 20 CRC patients and 20 healthy controls; subsequently, solid-phase microextraction-gas chromatography/mass spectrometry (SPME-GC/MS) was used to assess the exhaled volatile organic compounds (VOCs) of the study participants. The statistical methods of principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA) were performed to process the final data. The VOCs in the exhalations of CRC patients exhibited significant differences from the VOCs in the exhalations of healthy controls; in particular, relative to the latter exhalations, the former exhalations contain significantly higher levels of cyclohexanone, 2,2-dimethyldecane, dodecane, 4-ethyl-1-octyn-3-ol, ethylaniline, cyclooctylmethanol, trans-2-dodecen-1-ol, and 3-hydroxy-2,4,4-trimethylpentyl 2-methylpropanoate but significantly lower levels of 6-t-butyl-2,2,9,9-tetramethyl-3,5-decadien-7-yne (P < 0.05). Analyses of breath VOCs provide a related model of CRC exhalation that could represent an effective and convenient screening method for this disease.

Heparin therapy reduces 28-day mortality in adult severe sepsis patients: a systematic review and meta-analysis.

INTRODUCTION: There are approximately 19 million new cases of sepsis worldwide each year. Among them, more than one quarter of patients die. We aimed to assess the effects of heparin on short-term mortality in adult patients with sepsis and severe sepsis. METHODS: We searched electronic databases (Medline, Embase, and Cochrane Library databases; the Cochrane Controlled Trials Register) and conference proceedings (Web of Knowledge (Conference Proceedings Citation Index - Science, Conference Proceedings Citation Index - Social Sciences & Humanities)) from inception to July 2014, expert contacts and relevant websites. Controlled trials of heparin versus placebo in sepsis or severe sepsis were identified. In total two reviewers independently assessed eligibility, and four authors independently extracted data; consensus was reached by conference. We used the chi-square test and I2 to assess statistical heterogeneity (P <0.05). The primary analysis was based on the fixed-effect model to produce pooled odds ratios with 95% confidence intervals. RESULTS: A total of nine publications were included in the meta-analysis. Heparin decreased 28-day mortality (n = 3,482, OR = 0.656, 95% CI = 0.562 to 0.765, P <0.0001). According to the meta-analysis of 28-day mortality, heterogeneity was not found among the eight randomized clinical trials (RCTs) (I2 = 0.0%). Heparin had no effect on bleeding events in sepsis (seven RCTs, n = 2,726; OR = 1.063; 95% CI = 0.834 to 1.355; P = 0.623; and I2 = 20.9%). Subgroup analysis demonstrated that the sample size may be a source of heterogeneity, but experimental design was not. CONCLUSIONS: Heparin may reduce 28-day mortality in patients with severe sepsis, at the same time, there was no increase in the risk of bleeding in the heparin group. We recommend the use of heparin for sepsis and severe sepsis.

Low-dose hydrocortisone therapy attenuates septic shock in adult patients but does not reduce 28-day mortality: a meta-analysis of randomized controlled trials.

BACKGROUND: The role of low-dose hydrocortisone in attenuating septic shock and reducing short-term mortality in adult patients with septic shock is unclear. We conducted a meta-analysis of previous studies to determine whether hydrocortisone could ameliorate the effects of septic shock at 7 and 28 days and reduce 28-day morality. METHODS: Randomized controlled trials (RCTs) of corticosteroids versus placebo (or supportive treatment alone) were retrieved from electronic searches (Medline, Embase, and Cochrane Library databases; LILACS; and Web of Knowledge) and manual searches (up to May 2012). From a pool of 1949 potentially relevant articles, duplicate independent review identified 10 relevant, RCTs of low-dose hydrocortisone therapy in septic shock. Four pairs of reviewers agreed on the criteria for trial eligibility. One reviewer entered the data into the computer, and 3 reviewers checked the data. Missing data were obtained from the authors of the relevant trials. The primary outcome analyzed was an estimate of 28-day mortality. RESULTS: Eight publications were included in the meta-analysis. Low-dose hydrocortisone therapy did not reduce 28-day mortality (N = 1063; odds ratio (OR) = 0.891, 95% confidence interval (CI), 0.69-1.15). Low-dose hydrocortisone therapy ameliorated shock at 7 days (6 RCTs, N = 964, OR = 2.078, 95% CI, 1.58-2.73, P < 0.0001, and I = 26.9%) and 28 days (6 RCTs, N = 947, OR = 1.495, 95% CI, 1.12-1.99, P = 0.006, and I = 0.0%). CONCLUSIONS: Although low-dose hydrocortisone therapy ameliorates septic shock at 7 and 28 days, it does not reduce 28-day mortality.

Analysis of the volatile organic compounds of epidural analgesia-ameliorated metabolic disorder in pregnant women with gestational diabetes mellitus based on untargeted metabolomics.

Gestational diabetes mellitus (GDM) is a metabolic disease with an increasing annual incidence. Our previous observational study found that pregnant women with gestational diabetes had mild cognitive decline, which may be related to methylglyoxal (MGO). This study aimed to investigate whether labor pain aggravates the increase in MGO and explored the protective effect of epidural analgesia on metabolism in pregnant women with GDM based on solid-phase microextraction gas chromatography/mass spectrometry (SPME/GC-MS). Pregnant women with GDM were divided into a natural birth group (ND group, n = 30) and epidural analgesia group (PD group, n = 30). After fasting for ≥ 10 h overnight, venous blood samples were collected pre- and post-delivery to detect MGO, interleukin-6 (IL-6), and 8-epi-prostaglandin F2 alpha (8-iso-PGF2α) by ELISA. Serum samples were analyzed for volatile organic compounds (VOCs) using SPME-GC-MS. MGO, IL-6, and 8-iso-PGF2α levels in the ND group increased significantly post-delivery (P < 0.05) and were significantly higher in this group than the levels in the PD group (P < 0.05). Compared to the PD group, VOCs in the ND group increased significantly post-delivery. Further results indicated that propionic acid may be associated with metabolic disorders in pregnant women with GDM. Epidural analgesia can effectively improve the metabolism and immune function in pregnant women with GDM.

Measurement of exhaled breath temperature in patients under general anesthesia: A feasibility study.

The aim of the present study was to investigate the respiratory parameters that influence the exhaled breath temperature (EBT) and the feasibility of using the latter to monitor the core temperature under general endotracheal anesthesia. A total of 20 patients undergoing abdominal surgery were included in the present study. At the first stage of the experiment, the respiratory rate was adjusted, while the other respiratory parameters [tidal volume, inspiratory and expiratory time ratio (TI:TE), and positive end expiratory pressure (PEEP)] were maintained at a constant level. At the second stage, the tidal volume was adjusted, while the other respiratory parameters were maintained at a constant level. At the third stage, the TI:TE was adjusted, while the other parameters were maintained at a constant level. At the fourth stage, PEEP was adjusted, while the other parameters were maintained at a constant level. In each experiment, the EBT, the maximum temperature of exhaled air in each min, the inhaled air temperature and the nasopharyngeal temperature (T nose) were recorded every min. During the first stage of the experiment, no significant difference was noted in the EBT at different levels of respiratory rate. During the second, third and fourth stage, no significant difference was noted in the EBT at different tidal volumes, TI:TE and PEEP, respectively. The EBT was significantly correlated with the T nose. Overall, the present study demonstrated that the EBT of patients undergoing abdominal surgery under general endotracheal anesthesia was not affected by the examined respiratory parameters and that it could be considered a feasible method of monitoring core temperature.

Sofnolime with different water content causes different effects in two sevoflurane inhalational induction techniques with respect to the output of compound-A.

OBJECTIVE: During sevoflurane anesthesia with Sofnolime for CO(2) absorption, the factors affecting the production of compound A (a chemical is nepherotoxic) are still not clear. This study is designed to investigate the effects of different fresh gas flow during induction, the vital capacity induction (VCI) vs. the tidal volume breath induction (TBI) on the compound-A production with a fresh Sofnolime or a dehydrated Sofnolime using a simulated lung model. METHOD: The experiments were randomly divided into four groups: group one, VCIf, vital capacity fresh gas inflow with fresh Sofnolime; group two, TBIf, tidal volume breath fresh gas inflow with fresh Sofnolime; group three, VCId, vital capacity fresh gas inflow with dehydrated Sofnolime, and group four, TBId, tidal volume breath fresh gas inflow with dehydrated Sofnolime. The inspired sevoflurane was maintained at 8%, the concentrations of compound-A were assayed using Gas-spectrum technique, and Sofnolime temperatures were monitored at 1-min intervals throughout the experiment. RESULTS: The mean and maximum concentrations of compound A were significantly higher in the vital capacity group than the tidal volume breath group (P<0.01). At the beginning of anesthesia maintenance, the compound-A concentration in group VCIf was 36.28±6.13 ppm, which was significantly higher than the 27.32±4.21 ppm observed in group TBIf (P<0.01). However, these values decreased to approximately 2 ppm in the dehydrated Sofnolime groups. Sofnolime temperatures increased rapidly in the dehydrated Sofnolime groups but slowly in the fresh Sofnolime groups. CONCLUSION: With fresh Sofnolime, vital capacity induction increased compound-A production in the circuit system compared with tidal volume breath induction. However, with dehydrated Sofnolime, the effects of the two inhalation induction techniques on compound-A output were not significantly different.