The eicosanoid metabolic pathway is responsible for mediating the production of various inflammatory factors that are closely related to the development and resolution of inflammation. In biological matrices, the major quantifying obstacles were shown to be the oxidation and low quantities of eicosanoids and their metabolites. This study aimed to develop a reliable, sensitive ultrahigh-performance liquid chromatography coupled to a tandem mass spectrometry (UPLC-MS/MS) method to quantify eicosanoids in human serum. Solid-phase extraction (SPE) was used for sample preparation. The approach employed continuous ionization polarity switching. The target eicosanoids showed good linearity over the investigated concentration range (r2 > 0.99). The recovery rates were over 64.5%, and the matrix effects ranged from 73.0 to 128.0%. The limits of quantification were 0.048 ~ 0.44 ng/mL. For the broad concentration range, the CV % for accuracy and precision were less than ± 20%. We successfully applied this method to rapidly analyse 74 serum samples from severe influenza pneumonia, severe bacterial pneumonia and healthy individuals. Eicosanoid-related metabolite concentrations were quantified within a range similar to those of previously published articles. Compared to healthy individuals, our application found that 20-HETE, 14,15-EET and 11,12-EET were upregulated in severe influenza pneumonia patients, while LTB4 was downregulated. 8-HETE and 5-HETE were upregulated in severe bacterial pneumonia patients, while LTE4 was downregulated. This approach provides a means for monitoring the low quantities of eicosanoids in biological matrices, and our finding that different characteristic metabolite profiles may help discriminate the induction of severe pneumonia patients.
Abstract BACKGROUND Septic shock is a life-threatening subset of sepsis, and blood urea nitrogen (BUN) and serum albumin are inexpensive and easily available biomarkers. BUN to serum albumin ratio (BAR) has been identified as a valuable prognostic marker in various diseases. Therefore, we conducted a retrospective study to explore the relationship between BAR and mortality risk in septic shock. METHODS From 2008 to 2019, we enrolled 3, 220 patients diagnosed with septic shock from the MIMIC-IV database. Restricted cubic spline (RCS) was used to visualize the relationship between BAR and mortality. Kaplan-Meier survival curves were generated to evaluate differences in survival rates among three groups: low-BAR (<9.6), medium-BAR (≥9.6, <20.0), and high-BAR (≥20.0). Box plot analysis was performed to compare the distribution of BAR between survivors and non-survivors. Cox regression analysis was used to estimate the independent association between BAR and all-cause mortality. The receiver operating characteristic (ROC) curve analysis was conducted to assess the performance of BAR for predicting mortality. RESULTS The mean age was 66.1 years. The 28-day mortality risk increased non-linearly with BAR values as shown by RCS. Compared to the low-BAR or medium-BAR group, the high-BAR group had significantly higher mortality according to Kaplan-Meier curves for in-hospital, 28-day, 90-day, and 1-year mortalities. The boxplot demonstrated that patients who survived had lower BAR compare to non-survived in terms of in-hospital, 28-day, 90-day, and 1-year. The results of both the univariate and multivariate Cox regression analysis showed that BAR was an independent risk factor for predicting in-hospital, 28-day, 90-day, and 1-year mortalities, with higher BAR values associated with increasing mortality. For sensitivity analysis, the Cox regression analysis also showed that compared with the low-BAR group, the high-BAR group had a higher risk of in-hospital, 28-day, 90-day, and 1-year mortality rates in both the unadjusted and adjusted models. Conclusions The study showed that BAR was an independent risk factor for predicting both short-term and 1-year mortality rates in septic shock patients.
Abstract To inform seroepidemiological studies, we characterized the IgG‐ responses in COVID‐19 patients against the two major SARS‐CoV‐2 viral proteins, spike (S) and nucleocapsid (N). We tested 70 COVID‐19 sera collected up to 85 days post‐symptom onset and 230 non‐COVID‐19 sera, including 27 SARS sera from 2003. Although the average SARS‐CoV‐2 S and N‐IgG titers were comparable, N‐responses were more variable among individuals. S‐ and N‐assay specificity tested with non‐COVID‐19 sera were comparable at 97.5% and 97.0%, respectively. Therefore, S will make a better target due to its lower cross‐reactive potential and its' more consistent frequency of detection compared to N.
Objective
To investigate the effects of sufentanil on stress hormone and hemodynamic parameters in patients with sepsis in ICU.
Methods
A prospective randomized controlled study was carried out to select 46 patients with sepsis admitted to the ICU of Guangzhou Red Cross Hospital from October 2014 to August 2016. The patients were randomly divided into the control group (group C), fentanyl group (group F) and sufentanil group (group S). Patients in group C were given active treatment of the primary disease, and anti-infection, nutritional support, maintenance of electrolyte balance and other comprehensive treatment. Patients in group F and group S were treated in the same way as group C, while fentanyl and sufentanil were applied separately into them. The analgesic goal was behavioral pain scale (BPS) ≤3 points. The changes of stress hormone [adrenocorticotropic hormone (ACTH), glucocorticoids (GC), norepinephrine (NE) and epinephrine (E)] and hemodynamic parameters [heart rate (HR), mean arterial pressure (MAP) and central venous pressure (CVP)] before and after treatment were compared, and adverse drug reactions were recorded. The quantitative data were compared by analysis of variance or t test, and the repeated measurement data were analyzed by repeated measures analysis of variance. The enumeration data were compared by Chi-square test or Fisher exact probability method.
Results
There were no significant changes in the levels of NE and E before treatment and at 2 and 6 h after the treatment in the three groups (P>0.05). Compared with before treatment, there were no significant changes in ACTH and GC levels at 2 and 6 h after treatment in group C (P>0.05), and ACTH and GC levels decreased in group F and group S at 2 and 6 h after treatment (P 0.05). Compared with before treatment, the levels of HR were decreased at 2 and 6 h after the treatment in the three groups (P 0.05). Compared with before treatment, the levels of MAP increased in different degrees at 2 and 6 h after treatment in the three groups; Except for group F, there was significant difference between group C and group S (P 0.05).
Conclusions
Sufentanil has certain advantages in alleviating stress response in patients with sepsis in ICU. Its efficacy and safety are similar to that of fentanyl. What’ more, it has more stable hemodynamics.
Key words:
Sufentanil; Sepsis; Stress hormones; Hemodynamic
The current COVID-19 pandemic is posing a major challenge to public health on a global scale. While it is generally believed that severe COVID-19 results from over-expression of inflammatory mediators (i.e., a "cytokine storm"), it is still unclear whether and how co-infecting pathogens contribute to disease pathogenesis. To address this, we followed the entire course of the disease in cases with severe or critical COVID-19 to determine the presence and abundance of all potential pathogens present-the total "infectome"-and how they interact with the host immune system in the context of severe COVID-19.We examined one severe and three critical cases of COVID-19, as well as a set of healthy controls, with longitudinal samples (throat swab, whole blood, and serum) collected from each case. Total RNA sequencing (meta-transcriptomics) was performed to simultaneously investigate pathogen diversity and abundance, as well as host immune responses, in each sample. A Bio-Plex method was used to measure serum cytokine and chemokine levels.Eight pathogens, SARS-CoV-2, Aspergillus fumigatus (A. fumigatus), Mycoplasma orale (M. orale), Myroides odoratus (M. odoratus), Acinetobacter baumannii (A. baumannii), Candida tropicalis, herpes simplex virus (HSV) and human cytomegalovirus (CMV), identified in patients with COVID-19 appeared at different stages of the disease. The dynamics of inflammatory mediators in serum and the respiratory tract were more strongly associated with the dynamics of the infectome compared with SARS-CoV-2 alone. Correlation analysis revealed that pulmonary injury was directly associated with cytokine levels, which in turn were associated with the proliferation of SARS-CoV-2 and co-infecting pathogens.For each patient, the cytokine storm that resulted in acute lung injury and death involved a dynamic and highly complex infectome, of which SARS-CoV-2 was a component. These results indicate the need for a precision medicine approach to investigate both the infection and host response as a standard means of infectious disease characterization.
To investigate the protective effect of curcumin on hepatocytes in rats with sepsis.Eighty healthy male Sprague-Dawley (SD) rats were randomly divided into sham operation group, sepsis group, Xuebijing group and curcumin group (20 rats in each group) according to the random number table method. The animal model of sepsis was established by cecal ligation and puncture (CLP). In the sham operation group, the cecum was removed only after the operation. The rats in Xuebijing group and curcumin group were injected with 4 mL/kg Xuebijing, 100 mg/kg curcumin intraperitoneally at 0, 8 and 16 hours after operation (diluted with normal saline to 4 mL/kg) respectively; Sham operation group and sepsis group were injected with the same volume of normal saline. Five rats in each group were sacrificed at 2, 6, 12 and 24 hours after operation, the blood sample was collected, and liver tissues were harvested. The levels of serum procalcitonin (PCT), tumor necrosis factor-α (TNF-α) and interleukin (IL-6, IL-1β) were measured by enzyme linked immunosorbent assay (ELISA), the pathological changes of liver tissues were observed by hematoxylin-eosin (HE) staining, and apoptosis index (AI) was measured by TdT-mediated dUTP nick end labeling (TUNEL) method.The degree of hepatocyte injury in sepsis group increased gradually with time, the apoptotic cells gradually increased, and the AI of liver cells increased to 24 hours; serum levels of PCT, TNF-α, IL-6 and IL-1β were significantly higher than those in the sham operated group at 2 hours after operation and gradually increased to peak at 12 hours. The injury degree of liver tissue in Xuebijing group and curcumin group was significantly lighter than that in sepsis group, and the number of apoptotic cells were significantly decreased; the AI of hepatocytes and serum levels of PCT, TNF-α, IL-6 and IL-1β were significantly lower than those of sepsis group from 2 hours [AI: (11.89±1.34)%, (11.56±0.96)% vs. (23.59±2.00)% at 2 hours, (28.95±1.40)%, (30.35±1.20)% vs. (52.05±1.31)% at 24 hours; PCT (μg/L): 1.27±0.18, 1.13±0.19 vs. 2.41±0.21 at 2 hours, 5.07±0.45, 5.09±0.42 vs. 8.68±0.58 at 12 hours; TNF-α (ng/L): 127.93±9.53, 124.73±7.47 vs. 217.28±14.24 at 2 hours, 171.03±8.58, 168.68±6.95 vs. 314.13±14.39 at 12 hours; IL-6 (ng/L): 132.15±9.27, 136.14±8.42 vs. 153.35±12.64 at 2 hours, 211.65±8.52, 213.37±8.96 vs. 298.11±12.35 at 12 hours; IL-1β (ng/L): 33.59±1.49, 35.05±1.00 vs. 61.84±3.21 at 2 hours; 81.76±2.80, 84.06±3.42 vs. 132.24±2.58 at 12 hours, all P < 0.05]. There was no significant difference in the above indexes between Xuebijing group and curcumin group.Curcumin can inhibit the inflammatory response of hepatocytes in sepsis rats and reduce the apoptosis of hepatocytes, which can protect hepatocytes from sepsis.
Background: The current pandemic of COVID-19 is posing a major challenge to public health on a global scale. While it is generally believed severe COVID-19 results from over-expression of inflammatory mediators (i.e. a "cytokine storm"), it is still unclear whether and how co-infecting pathogens contribute to disease pathogenesis. To address this, we followed the entire course of disease in severe COVID-19 cases to reveal the presence and abundance of all potential pathogens present - the total "infectome" - and how they interact with the host immune system in the context of severe COVID-19 disease.Methods: We considered one severe and three critical cases of COVID-19, as well as a set of healthy controls, with longitudinal samples (throat swab, whole blood and serum) taken in each case. Total RNA sequencing (meta-transcriptomics) was performed to simultaneously reveal pathogen diversity and abundance, as well as host immune responses, within each sample. A Bio-Plex method was used to measure serum cytokine and chemokine levels.Findings: Eight pathogens were identified in these COVID-19 patients - Aspergillus fumigatus, Mycoplasma orale, Myroides odorantus, Acinetobacter baumannii, Candida tropicalis, herpes simplex virus and human cytomegalovirus - that appeared at different stages of disease course. Notably, the dynamics of inflammatory mediators in the serum as well as respiratory tract were better associated with the dynamics of the infectome as a whole rather than SARS-CoV-2 alone. Correlation analysis revealed that pulmonary injury was directly associated with cytokine levels, which in turn was associated with the proliferation of SARS-CoV-2 and the co-infecting pathogens.Interpretation: The cytokine storm that resulted in aggravated acute lung injury and death involved the highly complex and dynamic entire infectome of each patient, of which SARS-CoV-2 was a component. These results call for a precision-medicine approach to investigating both the infection and the host response on a daily basis as a standard means of infectious disease characterization.Funding: Guangzhou Institute of Respiratory Health Open Project (Funds provided by China Evergrande Group) - Project No. (2020GIRHHMS01), Guangdong Province "Pearl River Talent Plan" Innovation and Entrepreneurship Team Project (2019ZT08Y464), Macao Science and Technology Development Fund (0042/2020/A), Science research project of the Guangdong Province (2019B030316028), Special Project for Scientific and Technological Development and Emergency Response in COVID-19 Prevention and Control of Guangdong Province (2020A111129028), Special Project for Research and Promotion of Prevention and Control Techniques of COVID-19 and Emergency Response in Dongguan City (202071715001114), Jack Ma Foundation (2020-CMKYGG-02), Guangzhou Medical University High-level University Clinical Research and Cultivation Program ([2017] 159 and 160) and ARC Australian Laureate Fellowship (FL170100022).Declaration of Interests: We declare no competing interests.Ethics Approval Statement: The ethics committee of the FAHGMU (Ethics No. 2020-85) and Dongguan's People's Hospital (KYKT2020-005-A1) approved the sampling procedure and the use of patient samples for this study. Informed consent was obtained from each patient.
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