A patient's infectivity is determined by the presence of the virus in different body fluids, secretions, and excreta. The persistence and clearance of viral RNA from different specimens of patients ...with 2019 novel coronavirus disease (COVID-19) remain unclear. This study analyzed the clearance time and factors influencing 2019 novel coronavirus (2019-nCoV) RNA in different samples from patients with COVID-19, providing further evidence to improve the management of patients during convalescence.
The clinical data and laboratory test results of convalescent patients with COVID-19 who were admitted to from January 20, 2020 to February 10, 2020 were collected retrospectively. The reverse transcription polymerase chain reaction (RT-PCR) results for patients' oropharyngeal swab, stool, urine, and serum samples were collected and analyzed. Convalescent patients refer to recovered non-febrile patients without respiratory symptoms who had two successive (minimum 24 h sampling interval) negative RT-PCR results for viral RNA from oropharyngeal swabs. The effects of cluster of differentiation 4 (CD4)+ T lymphocytes, inflammatory indicators, and glucocorticoid treatment on viral nucleic acid clearance were analyzed.
In the 292 confirmed cases, 66 patients recovered after treatment and were included in our study. In total, 28 (42.4%) women and 38 men (57.6%) with a median age of 44.0 (34.0-62.0) years were analyzed. After in-hospital treatment, patients' inflammatory indicators decreased with improved clinical condition. The median time from the onset of symptoms to first negative RT-PCR results for oropharyngeal swabs in convalescent patients was 9.5 (6.0-11.0) days. By February 10, 2020, 11 convalescent patients (16.7%) still tested positive for viral RNA from stool specimens and the other 55 patients' stool specimens were negative for 2019-nCoV following a median duration of 11.0 (9.0-16.0) days after symptom onset. Among these 55 patients, 43 had a longer duration until stool specimens were negative for viral RNA than for throat swabs, with a median delay of 2.0 (1.0-4.0) days. Results for only four (6.9%) urine samples were positive for viral nucleic acid out of 58 cases; viral RNA was still present in three patients' urine specimens after throat swabs were negative. Using a multiple linear regression model (F = 2.669, P = 0.044, and adjusted R = 0.122), the analysis showed that the CD4+ T lymphocyte count may help predict the duration of viral RNA detection in patients' stools (t = -2.699, P = 0.010). The duration of viral RNA detection from oropharyngeal swabs and fecal samples in the glucocorticoid treatment group was longer than that in the non-glucocorticoid treatment group (15 days vs. 8.0 days, respectively; t = 2.550, P = 0.013) and the duration of viral RNA detection in fecal samples in the glucocorticoid treatment group was longer than that in the non-glucocorticoid treatment group (20 days vs. 11 days, respectively; t = 4.631, P < 0.001). There was no statistically significant difference in inflammatory indicators between patients with positive fecal viral RNA test results and those with negative results (P > 0.05).
In brief, as the clearance of viral RNA in patients' stools was delayed compared to that in oropharyngeal swabs, it is important to identify viral RNA in feces during convalescence. Because of the delayed clearance of viral RNA in the glucocorticoid treatment group, glucocorticoids are not recommended in the treatment of COVID-19, especially for mild disease. The duration of RNA detection may relate to host cell immunity.
Background Fluid therapy for severe acute pancreatitis （SAP） should not only resolve deficiency of blood volume, but also prevent fluid sequestration in acute response stage. Up to date, there has ...not a strategy for fluid therapy dedicated to SAP. So, this study was aimed to investigate the effects of fluid therapy treatment on prognosis of SAP. Methods Seventy-six patients were admitted prospectively according to the criteria within 72 hours of SAP onset. They were randomly assigned to a rapid fluid expansion group （Group I, n=36） and a controlled fluid expansion group （Group II n=-40）. Hemodynamic disorders were either quickly （fluid infusion rate was 10-15 ml.kg-1-h-1, Group I） or gradually improved （fluid infusion rate was 5-10 ml-kg1.h-1, Group II） through controlling the rate of fluid infusion. Parameters of fluid expansion, blood lactate concentration were obtained when meeting the criteria for fluid expansion. And APACHE II scores were obtained serially for 72 hours. Rate of mechanical ventilation, incidence of abdominal compartment syndrome （ACS）, sepsis, and survival rate were obtained. Results The two groups had statistically different （P 〈0.05） time intervals to meet fluid expansion criteria （Group I, 13.5±6.6 hours; Group II, （24.0±5.4） hours）. Blood lactate concentrations were both remarkably lower as compared to the level upon admission （P 〈0.05） and reached the normal level in both groups upon treatment. It was only at day 1 that hematocrit was significantly lower in Group I （35.6%±6.8%） than in Group II （38.5%±5.4%） （P〈0.01）. Amount of crystalloid and colloid in group I （（4028±1980）ml and （1336±816）ml） on admission day was more than those of group II （（2472±1871）ml and （970±633）ml）. No significant difference was found in the total amount of fluids within four days of admission between the two groups （P〉0.05）. Total amount of fluid sequestration within 4 days was higher in Group I （（5378±2751）ml） than in Group II （（4215±1998）ml, P 〈0.05）. APACHE II scores were higher in Group I on days 1, 2, and 3 （P〈0.05）. Rate of mechanical ventilation was higher in group I （94.4%） than in group II （65%, P〈0.05）. The incidences of abdominal compartment syndrome （ACS） and sepsis were significantly lower in Group II （P 〈0.05）. Survival rate was remarkably lower in Group I （69.4%） than in Group II （90%, P〈0.05）. Conclusions Controlled fluid resuscitation offers better prognosis in patients with severe volume deficit within 72 hours of SAP onset. Chin Med J 2009; 122（2）： 169-173
It has been reported that approximately 40% of ALI (acute lung injury) incidence resulted from sepsis. Paclitaxel, as a classic anti-cancer drug, plays an important role in the regulation of ...inflammation. However, we do not know whether it has a protective effect against CLP (cecal ligation and puncture)-induced septic ALI. Our study aims to illuminate the mitigative effects of paclitaxel on sepsis-induced ALI and its relevant mechanisms.
The survival rates and organ injuries were used to evaluate the effects of paclitaxel on CLP mice. The levels of inflammatory cytokines were tested by ELISA. MUC1 siRNA pre-treatment was used to knockdown MUC1 expression in vitro. GO203 was used to inhibit the homodimerization of MUC1-C in vivo. The expression levels of MUC1, TLR 4 and p-NF-κB/p65 were detected by Western blot.
Our results showed that paclitaxel improved the survival rates and ameliorated organ injuries especially lung injury in CLP-induced septic mice. These were accompanied by reduced inflammatory cytokines in sera and BALF (bronchoalveolar lavage fluid). We also found paclitaxel could attenuate TLR 4-NF-κB/p65 activation both in lung tissues of septic mice and LPS-stimulated lung type II epithelial cell line A549. At the upstream level, paclitaxel-upregulated expression levels of MUC1 in both in vivo and in vitro experiments. The inhibitory effects of paclitaxel on TLR 4-NF-κB/p65 activation were reversed in lung tissues of septic mice pre-treated with MUC1 inhibitor and in MUC1-knockdown A549 cells. Protection of paclitaxel on sepsis-induced ALI and decrease of inflammatory cytokines were also abolished by inhibition of MUC1.
Collectively, these results indicated paclitaxel could significantly alleviate acute lung injury in CLP-induced septic mice and LPS-stimulated lung type II epithelial cell line A549 by activating MUC1 and suppressing TLR-4/NF-κB pathway.
Background Hemoconcentration may be an important factor that determines the progression of severe acute pancreatitis （SAP）. In addition, it has been proposed that biomarkers may be useful in ...predicting subsequent necrosis in SAP. However, it is still uncertain whether hemodilution in a short term can improve outcome. We aimed to investigate the effect of rapid hemodilution on the outcome of patients with SAP. Methods One hundred and fifteen patients were admitted prospectively according to the criteria within 24 hours of SAP onset. Patients were randomly assigned to either rapid hemodilution （hematocrit （HCT） 〈35%, n=56） or slow hemodilution （HCT 〉35%, n=-59） within 48 hours of onset. Balthazar CT scores were calculated on admission, day 7, and day 14, after onset of the disease. Time interval for sepsis presented, incidence of sepsis within 28 days and in-hospital survival rate were determined. Results The amount of fluid used in rapid hemodilution was significantly more than that used in slow hemodilution （P 〈0.05） on the admission day, the first day, and the second day. There were significant differences between the rapid and slow hemodilution group in terms of hematocrit, oxygenation index, pH values, APACHE II scores and organ dysfunction at different time during the first week. There were significant differences in the time interval to sepsis in rapid hemodilution （（7.4±1.9） days） compared with the slow hemodilution group （（10.2±2.3） days）, and the incidence of sepsis （78.6%） was higher in the rapid group compared to the slow （57.6%） in the first 28 days. The survival rate of the slow hemodilution group （84.7%） was better than the rapid hemodilution （66.1%. P 〈0.05）. Conclusions Rapid hemodilution can increase the incidence of sepsis within 28 days and in-hospital mortality. Hematocrit should be maintained between 30%-40% in the acute response stage.
Cryptococcal meningitis (CM) is a fatal fungal central nervous system (CNS) infection caused by
Cryptococcus
infecting the meninges and/or brain parenchyma, with fever, headache, neck stiffness, and ...visual disturbances as the primary clinical manifestations. Immunocompromised individuals with human immunodeficiency virus (HIV) infection or who have undergone organ transplantation, as well as immunocompetent people can both be susceptible to CM. Without treatment, patients with CM may have a mortality rate of up to 100% after hospital admission. Even after receiving therapy, CM patients may still suffer from problems such as difficulty to cure, poor prognosis, and high mortality. Therefore, timely and effective treatment is essential to improve the mortality and prognosis of CM patients. Currently, the clinical outcomes of CM are frequently unsatisfactory due to limited drug choices, severe adverse reactions, drug resistance, etc. Here, we review the research progress of CM treatment strategies and discuss the suitable options for managing CM, hoping to provide a reference for physicians to select the most appropriate treatment regimens for CM patients.
Sepsis remains a major global concern and is associated with high mortality and morbidity despite improvements in its management. Markers currently in use have shortcomings such as a lack of ...specificity and failures in the early detection of sepsis. In this study, we aimed to identify key genes involved in the molecular mechanisms of sepsis and search for potential new biomarkers and treatment targets for sepsis using bioinformatics analyses. Three datasets (GSE95233, GSE57065, and GSE28750) associated with sepsis were downloaded from the public functional genomics data repository Gene Expression Omnibus. Differentially expressed genes (DEGs) were identified using R packages (Affy and limma). Functional enrichment of the DEGs was analyzed with the DAVID database. Protein-protein interaction networks were derived using the STRING database and visualized using Cytoscape software. Potential biomarker genes were analyzed using receiver operating characteristic (ROC) curves in the R package (pROC). The three datasets included 156 whole blood RNA samples from 89 sepsis patients and 67 healthy controls. Between the two groups, 568 DEGs were identified, among which 315 were upregulated and 253 were downregulated in the septic group. These genes were enriched for pathways mainly involved in the innate immune response, T-cell biology, antigen presentation, and natural killer cell function. ROC analyses identified nine genes—LRG1, ELANE, TP53, LCK, TBX21, ZAP70, CD247, ITK, and FYN—as potential new biomarkers for sepsis. Real-time PCR confirmed that the expression of seven of these genes was in accordance with the microarray results. This study revealed imbalanced immune responses at the transcriptomic level during early sepsis and identified nine genes as potential biomarkers for sepsis.
Background. Ferroptosis is a nonapoptotic form of programmed cell death, which may be related to the occurrence and development of sepsis-induced acute respiratory distress syndrome (ARDS)/acute lung ...injury (ALI). Mucin 1 (MUC1) is a kind of macromolecule transmembrane glycoprotein. Previous studies have shown that MUC1 could relieve ALI in sepsis and predict whether sepsis patients would develop into ARDS. However, the role of MUC1 in the ferroptosis of sepsis-induced ALI/ARDS remains unclear. Materials and Methods. Sera samples from 50 patients with sepsis/septic shock were used to detect iron metabolism-related markers. Western blot and qRT-PCR were conducted to detect the expression levels of ferroptosis-related genes. Enzyme-linked immunosorbent assay (ELISA) was performed to evaluate inflammatory factors. Transmission electron microscopy (TEM) was used to assess morphological changes of cells. Results. The results showed that the iron metabolism-related indicators in sepsis-induced ARDS patients changed significantly, suggesting the iron metabolism disorder. The expression levels of ferroptosis-related genes in lung tissues of sepsis had marked changes, and the lipid peroxidation levels increased, while Ferrostatin-1 (Fer-1) could reverse the above results, which confirmed the occurrence of ferroptosis. In terms of mechanism studies, inhibition of MUC1 dimerization could increase the expression level of Keap1, reduce the phosphorylation level of GSK3β, inhibit the entry of Nrf2 into the nucleus, further inhibit the expression level of GPX4, enhance the lipid peroxidation level of lung tissues, trigger ferroptosis, and aggravate lung injury. Besides, inhibiting MUC1 reversed the alleviating effect of vitamin E on ALI caused by sepsis, increased the aggregation of inflammatory cells in lung tissues, and aggravated alveolar injury and edema. Conclusions. Our study was the first to explore the changes of iron metabolism indicators in ALI/ARDS of sepsis, clarify the important role of ferroptosis in ALI/ARDS induced by sepsis, and reveal the effects and specific mechanisms of MUC1 in regulating ferroptosis, as well as the sensitization on vitamin E.
This study aimed to investigate whether free fatty acids (FFAs) could induce the release of neutrophil extracellular traps (NETs), as well as the mechanism of FFAs-induced NETs in acute lung injury ...(ALI). FFAs were used to induce NETs production. The reactive oxygen species (ROS) production was detected after FFA and NADPH oxidase inhibitor treatments. The association between FFAs-induced NETs and the activation of p38, ERK, and JNK pathways was investigated. The effect of FFAs-induced NETs on the dendritic cells (DCs) activation and T cell differentiation was investigated. FFAs could induce neutrophils to produce NETs. FFAs significantly promoted ROS production and increased the expression of ERK, p38 and JNK, and treatment of the inhibitors of NAPDH oxidase (DPI), p38 (SB202190), ERK1/2 (U0126) and JNK (SP600125) inhibited FAAs-induced NETs production. FFAs induced NETs could promote DCs activation and consequently led to the differentiation of primary CD4+ T cells into Th1 and Th17 cells and the release of IL-1β, IL-12 and TNF-α. FFAs are capable of inducing NETs via NOX, ERK, p38 and JNK pathways. FFA-induced NETs further lead to DCs activation and T cell differentiation, which can well explain the mechanism of ALI caused by FFAs.
Purpose
A population-level description and analysis of sepsis-related mortality in China is key to the planning and assessment of interventional strategies.
Methods
Retrospective analysis of multiple ...cause of death (MCOD) recorded in the population-based national mortality surveillance system (NMSS) of China. All sepsis-related deaths occurring in 605 disease surveillance points (DSPs) covering 323.8 million population across China were included in our study. Age-standardized mortality and national estimate of sepsis-related deaths were estimated using the census population in 2010 and 2015, respectively.
Results
In 2015, a total of 1,937,299 deaths occurring in any of the 605 DSPs and standardized sepsis-related mortality rate was 66.7 (95% confidence interval CI 66.4–67.0) deaths per 100,000 population. This produced a national estimate of 1,025,997 sepsis-related deaths. Sepsis-related mortality rates exhibited significant geographic variation. In multilevel analysis, male sex (rate ratio RR 1.582, 95% CI 1.570–1.595), increasing age (RR 1.914 for 5-year group, 95% CI 1.910–1.917), and presence of comorbidity (RR 2.316, 95% CI 2.298–2.335) were independently associated with increased sepsis-related mortality. Higher disposable income (RR 0.717 for the fourth interquartile range vs. the first interquartile range, 95% CI 0.515–0.978) and mean years of education (RR 0.808 for the fourth interquartile range vs. the first interquartile range, 95% CI 0.684–0.955) were negatively associated with sepsis-related mortality. However, population-based hospital doctors were not significantly associated with sepsis-related mortality.
Conclusions
The standardized sepsis-related mortality rate in China was high and varied according to socioeconomic indices, even though some uncertainty remained.
•Inhibition of MUC1 could aggravate sepsis-induced acute lung injury.•MUC1 could inhibit activation of TLR-4 by stabilizing HIF-1α in sepsis-induced acute lung injury.•Plasma MUC1 levels had great ...predictive value for occurrence of ARDS in sepsis patients.
We aimed to investigate whether inhibition of MUC1 would aggravate sepsis-induced ALI, and explore the predictive value of plasma MUC1 for sepsis patients with or without ARDS.
MUC1 siRNA pre-treatment was used to knockdown MUC1 expression in vitro. GO203 was used to inhibit the homodimerization of MUC1-C in vivo. Expression levels of MUC1, TLR 4 and HIF-1α were detected by Western blot. In addition, plasma MUC1 levels of enrolled patients were detected by ELISA on the day of admission and on the 3rd day. ROC curve was used to determine the predictive value of MUC1 in sepsis patients with ARDS.
Our results showed that inhibition of MUC1 could aggravate sepsis-induced acute lung injury and increase the expression of inflammatory cytokines in sera and BALF of sepsis mice. At the same time, we confirmed that inhibition of MUC1 could significantly decrease HIF-1α expression and thereby activate the expression level of TLR4. HIF-1α was a negative regulator of TLR-4. In addition, plasma MUC1 levels of sepsis patients with ARDS were significantly higher than those without ARDS and healthy adults. ROC curve showed that predictive value of plasma MUC1 on sepsis with ARDS on the 3rd day of enrollment was higher than the day of enrollment.
MUC1 could inhibit the expression of TLR-4 by stabilizing HIF-1α, thereby alleviate sepsis-induced lung injury and protect organ function. At the same time, elevated MUC1 levels in plasma had a good predictive valud on whether patients with sepsis would develop ARDS.
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