Background:Among critically ill patients in the intensive care unit (ICU), sepsis is an urgent global public health problem due to its high incidence, high mortality rate and complex pathogenesis. Objective:This study was to evaluate the predictive value of neutrophil-to-lymphocyte ratio (NLR), and neutrophil-to-lymphocyte and platelet ratio (NLPR) in-hospital mortality in septic patients on days 1, 3 and 5 in ICU. Methods:The data of septic patients admitted to the ICU of the Sixth Affiliated Hospital of Sun Yat-sen University from March, 2018 to July, 2019 were collected. NLR and NLPR were calculated and multivariate logistic regression analysis was performed to identify the relationship between them and in-hospital mortality, respectively. Receiver operating characteristic curve (ROC) was used to determine the efficacy and optimal cutoff value of diagnostic tests. Results:A total of 173 septic patients were included in this analysis, including 108 cases in the survival group and 65 in the death group, with a total mortality rate of 37.6%. A multivariate logistic regression analysis showed that NLR on day 5 was independently correlated with in-hospital mortality rate (OR 1.041, 95% CI: 1.008-1.074), and Day 5 NLPR was also independently associated with in-hospital mortality rate (OR 1.020, 95% CI: 1.001-1.040). The areas under the receiver operating characteristic curve (AUC) of the NLR on days 1 and 3 was 0.513 and 0.542 respectively, and the optimal cutoff value were 23.16 and 15.48, and the AUC of the NLR on day 5 was 0.589, and the best cutoff value was 15.85. The AUC of NLPR on day 1 and 3 was 0.517 and 0.547, respectively, and the optimal cutoff value was 10.25 and 18.47. The AUC of NLPR on day 5 was the largest, 0.654, and the optimal cutoff value was 8.22. After combined NLPR on day 5 with age and sequential organ failure assessment (SOFA) scores, the AUC increase to 0.718. Among the joint predictors, the optimal cutoff value for NLPR on day 5 was 9.31. Conclusion:We found that Day 5 NLPR and NLR were independently correlated with in-hospital mortality. Day 5 NLPR Combined with age and SOFA scores may be help predict mortality in ICU septic hospitalized patients.

OBJECTIVE:Sepsis is a life-threatening disease without ideal biomarkers. Some long non-coding RNAs (lncRNAs) are found to be implicated in sepsis. Thus, we investigated the effects of lncRNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) on inflammation in septic mice and the potential mechanisms of the MALAT1/microRNA-23a (miR-23a)/MCEMP1 axis.METHODS:The sepsis mice model was generated by cecal ligation and puncture (CLP). Then the expressions of lncRNA MALAT1, mast cell-expressed membrane protein 1 (MCEMP1), and miR-23a in septic mice were determined. The interaction between lncRNA MALAT1, miR-23a and MCEMP1 was confirmed. Loss- and gain-of-function approaches were used to verify the roles of the lncRNA MALAT1, miR-23a, and MCEMP1 in inflammation, cell proliferation and apoptosis in septic mice.RESULTS AND CONCLUSION:The myeloperoxidase (MPO) activity and the expression of interleukin 6 (IL-6), IL-1β, IL-10, and tumor necrosis factor-α (TNF-α) were detected. High expression of the lncRNA MALAT1 and MCEMP1, as well as low expression of miR-23a, was observed in septic mice. LncRNA MALAT1 competitively bound to miR-23a, and miR-23a targeted MCEMP1. Moreover, the down-regulation of lncRNA MALAT1 repressed the expression of MPO, IL-6, IL-10, TNF-α, and IL-1β. Silencing of lncRNA MALAT1 or overexpression of miR-23a reduced inflammation, inhibited cell proliferation, and promoted cell apoptosis in septic mice. Taken together, MALAT1 promotes the inflammation in septic mice by binding to miR-23a to up-regulate MCEMP1. Therefore, silencing of lncRNA MALAT1 might provide a novel therapeutic target for sepsis.

Corticosteroid is commonly used to reduce damage from inflammatory reactions in coronavirus disease 2019 (COVID-19). We aim to determine the outcomes of corticosteroid use in critically ill COVID-19 patients. Ninety six critically ill patients, hospitalized in 14 hospitals outside Wuhan from January 16 to March 30, 2020 were enrolled in this study. Among 96 critical patients, 68 were treated with corticosteroid (CS group), while 28 were not treated with corticosteroids (non-CS group). Multivariable logistic regression were performed to determine the possible correlation between corticosteroid use and the treatment outcomes. Forty-six (68%) patients in the CS group died compared to six (21%) of the non-CS group. Corticosteroid use was also associated with the development of ARDS, exacerbation of pulmonary fibrosis, longer hospital stay and virus clearance time. On admission, no difference in laboratory findings between the CS and the non-CS group was observed. After corticosteroid treatment, patients treated with corticosteroids were associated with higher counts of white blood cells, neutrophils, neutrophil-to-lymphocyte ratio, alanine aminotransferase level and Sequential Organ Failure Assessment score. In conclusion, corticosteroid use in critically ill COVID-19 patients was associated with a much higher case fatality rate. Frequent incidence of liver injury and multi-organ failure in corticosteroid treated patients may have contributed to the adverse outcomes. The multi-organ failure is likely caused by more persistent SARS-CoV-2 infection and higher viral load, due to the inhibition of immune surveillance by corticosteroid.

Objectives: Cathepsin B (CTSB), nod-like receptor family pyrin domain-containing 3 (NLRP3), and caspase-1 play an important role in the development of Acute Pancreatitis (AP). Besides, the relationship between the proteins remains poorly understood. In addition, whereas previous studies have found caspase-1 activation in AP, pyroptosis, a caspase-1 induced cell death mode, has never been proposed and proved in AP. Methods: We induced AP in mice by intraperitoneal injection of cerulein. Mice in the inhibitor group of CTSB were pretreated with injection of CA-074me, while mice in the inhibitor group of caspase-1 were of Ac-YVADCHO, 1 h earlier. We evaluated the inflammation of the pancreas and the detected expression of activated CTSB, NLRP3, ASC, caspase-1p20, IL-1 beta and IL-18. TUNEL staining was used to detect acinar cell death. Results: The inflammation of the pancreas in the two inhibitor groups was significantly reduced compared with that in the AP group. We observed that CA-074me not only inhibits CTSB, but also suppresses the expression and activity of NLRP3, ASC and caspase-1. We found that CA-074me further inhibits the downstream event of caspase-1, including pro-inflammatory cytokine secretion and pyroptosis. Whereas Ac-YVAD-CHO inhibited caspase-1 and decreased pro-inflammatory cytokine secretion and pyroptosis, it did not down-regulate the expression and activity of CTSB, NLRP3 and ASC. Conclusion: The results indicate that CTSB may aggravate AP by activating the NLRP3 inflammasome and promoting Caspase-1-induced pyroptosis. These provide clues about the pathophysiological mechanisms of AP, shedding light on new ideas and potential targets for the prevention and treatment of AP.

BACKGROUND:Sepsis is a systemic inflammatory response syndrome. MicroRNA (miRNA) plays an important role in immune cell activation, inflammatory cytokine release and immune response. However, the mechanism of miR-133a in sepsis remains largely unknown.METHODS:Sepsis mice models were established by applying the cecal ligation and puncture (CLP) method. Quantitative real-time polymerase chain reaction (qRT-PCR) assay was performed to detect the relative expression of miR-133a and inflammatory cytokines. Hematoxylin and eosin (H&E) staining and enzyme-linked immunosorbent assay (Elisa) were used to evaluate organ injury and inflammatory response. Besides, lipopolysaccharide (LPS)-induced RAW264.7 macrophages were used to construct sepsis cell models. Further, dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay were carried out to confirm the relationship between miR-133a and sirtuin-1 (SIRT1). In addition, western blot (WB) assay was performed to measure the relative SIRT1 protein level.RESULTS:MiR-133a was highly expressed in sepsis patients and CLP mice models. Knockdown of miR-133a inhibited sepsis-induced lung, liver and kidney injuries and inflammatory response in CLP mice models. Besides, miR-133a inhibitor also alleviated the inflammatory response of RAW264.7 macrophages induced by LPS. SIRT1 was a target of miR-133a, and silenced SIRT1 could reverse the anti-inflammatory effect of miR-133a inhibitor on LPS-induced sepsis cell models.CONCLUSION:MiR-133a promoted the inflammatory response of sepsis by inhibiting the expression of SIRT1, which might provide a new therapeutic strategy for sepsis.

In this study, we collected a total of 610 hospitalized patients from Wuhan between February 2, 2020, and February 17, 2020. We reported a potentially high false negative rate of real-time reverse-transcriptase polymerase chain reaction (RT-PCR) testing for SARS-CoV-2 in the 610 hospitalized patients clinically diagnosed with COVID-19 during the 2019 outbreak. We also found that the RT-PCR results from several tests at different points were variable from the same patients during the course of diagnosis and treatment of these patients. Our results indicate that in addition to the emphasis on RT-PCR testing, clinical indicators such as computed tomography images should also be used not only for diagnosis and treatment but also for isolation, recovery/discharge, and transferring for hospitalized patients clinically diagnosed with COVID-19 during the current epidemic. These results suggested the urgent needs for the standard of procedures of sampling from different anatomic sites, sample transportation, optimization of RT-PCR, serology diagnosis/screening for SARS-CoV-2 infection, and distinct diagnosis from other respiratory diseases such as fluenza infections as well.

Whether the intermediate care unit (IMCU) is beneficial for the oldest-old (aged ≥ 80 years) general surgical patients still remains unknown. We aimed to investigate the impacts of IMCU on the clinical outcomes and cost in this population. A retrospective, pre- and postintervention study was performed in this population in a university teaching hospital. The primary outcome was the occurrence of life-threatening complications including death or unplanned ICU admission after the surgeries. Secondary outcomes included the comparisons of the hospitalization expenses, the hospital length of stay (LOS) and the postoperative LOS between the pre-IMCU group and the IMCU group. Two hundred and seventeen patients were enrolled, including 98 in the pre-IMCU group and 119 in the IMCU group. After the introduction of IMCU, the occurrence of life-threatening complications significantly dropped from 11.2 to 2.5% (P = 0.012). The total hospitalization expenses showed a nonsignificant decreasing trend in the IMCU group (pre-IMCU group: 85856.3 ± 66583.7 RMB vs IMCU group: 78936.4 ± 36710.4 RMB). The treatment fee was much lower in the IMCU group (IMCU group: 4930.0 ± 4280.2 RMB vs pre-IMCU group: 7378.2 ± 10096.7 RMB, P = 0.017). Both the hospital LOS (IMCU group: 20.3 ± 10.3 days vs pre-IMCU group: 19.5 ± 9.0 days) and the postoperative hospital LOS (IMCU group: 12.0 ± 8.1 days vs pre-IMCU group: 11.2 ± 7.0 days) were not statistically different in the two groups. The allocation of the oldest-old surgical patients who do not need organ support therapy in the ICU to IMCU rather than in the standard wards was associated with a significant decrease in postoperative life-threatening complications and treatment fee. This study was registered at https://www.chictr.org.cn (ChiCTR2000030639).

BACKGROUND/AIMS:Intraoperative blood loss more than 400 mL during gastrointestinal surgery is an independent predictor of mortality. Desmopressin acetate (DDAVP) could reduce perioperative blood loss. Few studies have prompted concerning the effects of DDAVP on gastrointestinal surgery. This study was to investigate whether DDAVP can decrease blood loss in patients with massive hemorrhage undergoing gastrointestinal surgery. MATERIALS AND METHODS:A multiple-centers, double-blind clinical trial was conducted, patients who underwent gastrointestinal surgery were recruited from 3 hospitals, randomly assigned to two different groups. Patients in the treatment group received desmopressin 0.3 ug/kg,30 min once a day after surgery, patients in the control group received 50 ml saline for 30 min. The primary outcome was the changes of hemoglobin at 24 hours after the surgery. And the secondary outcomes included coagulation function, urine volume, serum creatinine, and safety. RESULTS:There were 59 patients enrolled between 1 June 2015 and 1 June 2017. At 24hr.after surgery, a decrease in hemoglobin in the DDAVP group was significantly lower than that in the NS group (-5.0±6.9 g/L vs. -10.2±9.3g/L, p=0.03). Sonoclot® showed that the platelet function in the DDAVP group was higher than that in NS group at 24 hr. (2.56 ±0.59 vs. 1.91 ±0.72, p<0.05). There was no difference in urine volume and serum creatinine at 24 hr. between two group. CONCLUSION:DDAVP could reduce post-operation blood loss in patients with massive hemorrhage undergoing surgery by improving the platelet function. We observed no difference in urine volume and serum creatinine in two groups.

Hypophosphatemia generally occurs in Intensive Care Units (ICUs), but its impact is often ignored. The aim of this study was to investigate whether hypophosphatemia can be a risk factor for ICU 28-day mortality. A single-center retrospective cohort study was conducted by collecting data from 1073 patients admitted to general ICU and then presented to the Sixth Affiliated Hospital, Sun Yat-sen University (Guangzhou City, Guangdong Province, China) from 1 January 2016 to 31 December 2017. The patients were divided into a normal control group (serum phosphate levels 0.80–1.60 mmol/L) and a hypophosphatemia group (serum phosphate levels < 0.80 mmol/L), based on the concentration of phosphorus at the time of ICU admission. The association between phosphate levels and ICU 28-day mortality was evaluated by binary logistic regression analysis. Multivariate logistic regression was employed to predict the ICU 28-day mortality. The cohort included 946 patients with a median phosphate concentration of 0.77 mmol/L (interquartile range 0.55–1.03 mmol/L). Patients with hypophosphatemia had a higher ICU 28-day mortality than the normal control group (33.3% vs 24.0%, P < 0.05). Patients with hypophosphatemia had a longer ICU and hospital stays, and prolonged duration of mechanical ventilation (all P < 0.05). Hypophosphatemia was an independent risk factor for ICU 28-day mortality (adjusted OR = 1.5, 95% CI = 1.1–2.1, P = 0.01) in the multivariate logistic regression analysis. Hypophosphatemia at admission is an independent risk factor for 28-day mortality in general ICU patients. The medical study was approved by the Institutional Ethics Committee of the Six Affiliated Hospital, Sun Yat-sen University (Approval number: 2017ZSLYEC-110). No consent was given as the data were analyzed anonymously.

The aim of the current study was to explore the roles of metabolomics in early diagnosis of sepsis by comparing blood and urine metabolites between sepsis patients and non-infected systemic inflammatory response syndrome (SIRS) patients. Seventeen sepsis patients and 13 non-infected SIRS patients were enrolled in this study. Blood and urine samples were collected from all patients and used for the detection of metabolomics using tandem mass spectrometry (MS/MS). Data were analyzed using specific analysis software and interpretation database. There were no differences in age, sex, and APACHEII scores between the two groups (P>0.05). Data from patient serum and urinary metabolites were normalized, then used for establishment of a 3-Diamensional map of the PCA model using specific software. This map showed a discrepancy between SIRS and sepsis groups. A total of 93 substances were detected in serum. According to importance of variable projection (VIP) rankings, there were 11 substances with VIP>1. Of these, aspartate, free carnitine, ornithine, and glutamic acid were increased, while valine, serine, and leucine were decreased (P<0.05). A total of 175 substances were determined in the urine samples, of which 16 substances were with VIP>1.4, according to the VIP ranking. Metabolomics, based on mass spectrometry, showed significant differences in blood and urine metabolites between non-infected SIRS patients and sepsis patients.