Blood urea nitrogen and clinical prognosis in patients with COVID-19: A retrospective study.

The aim of this study was to estimate the association between blood urea nitrogen (BUN) and clinical prognosis in patients with COVID-19. A multicenter, retrospective study was conducted in adult patients with COVID-19 in 3 hospitals in Zhenjiang from January 2023 to May 2023. Patients were divided into survival and death group based on whether they survived at day 28. The demographic, comorbidities, and laboratory data were independently collected and analyzed, as well as clinical outcomes. Total 141 patients were enrolled and 23 (16.3%) died within 28 days. Patients who died within 28 days had a higher level of BUN compared with survivors. Bivariate logistic regression analysis showed that BUN was a risk factor for 28-day mortality in patients with COVID-19. ROC curve showed that BUN could predict 28-day mortality of COVID-19 patients (AUC = 0.796, 95%CI: 0.654-0.938, P < .001). When the cutoff value of BUN was 7.37 mmol/L, the sensitivity and specificity were 84.62% and 70.31%. Subgroup analysis demonstrated that hyper-BUN (≥7.37 mmol/L) was associated with increased 28-day mortality among COVID-19 patients. Patients with COVID-19 who died within 28 days had a higher level of BUN, and hyper-BUN (≥7.37 mmol/L) was associated with increased 28-day mortality.

PFKFB3 promotes sepsis-induced acute lung injury by enhancing NET formation by CXCR4hi neutrophils.

CXCR4hi neutrophils, which are a subset of neutrophils with high CXCR4 expression, are important contributors to sepsis-induced acute lung injury (ALI). PFKFB3, a key glycolysis gene, plays an essential role in neutrophil inflammatory activation. However, the specific involvement of PFKFB3 in sepsis-induced ALI remains unclear. Here, we observed that PFKFB3 was upregulated in CXCR4hi neutrophils and facilitated sepsis-induced ALI. Mechanistically, we observed that PFKFB3 promoted sepsis-induced ALI by enhancing neutrophil extracellular trap (NET) formation by CXCR4hi neutrophils. Further study indicated that PFKFB3 promoted NET formation by upregulating glycolytic metabolism in CXCR4hi neutrophils. In summary, our study uncovered a new mechanism by which CXCR4hi neutrophils trigger sepsis-induced ALI by promoting NET formation, which is supported by PFKFB3-mediated glycolytic metabolism.

Assessment of hypokalemia and clinical prognosis in Patients with COVID-19 in Yangzhou, China.

BACKGROUND: Hypokalemia is a frequent electrolyte imbalance in patients with COVID-19. The aim of this study was to estimate the association between hypokalemia and clinical prognosis in patients with moderate COVID-19. METHODS: A single-center, retrospective, observational study was conducted on 81 non-ICU admitted patients with moderate COVID-19 according to the criteria issued by the Chinese Health Bureau in the Third People's Hospital of Yangzhou (Northern Jiangsu People's Hospital New District Branch) from 4th to 25th August 2021. The demographic, clinical, and laboratory data were reviewed and collected, then the correlation between hypokalemia and prognosis was determined. RESULTS: The level of serum potassium of patients ranged from 2.80 mmol/L to 4.70 mmol/L. Hypokalemia was detected in 39 out of the 81 included patients (48.15%) during hospitalization. Patients with hypokalemia had prolonged days of negative nucleic acid conversion and hospital stay. Correlation analysis showed that the level of serum potassium was negatively correlated with days of negative nucleic acid conversion and length of hospital stay. Bivariate logistic regression analysis proved that hypokalemia was a risk factor for prolonged hospital stay in patients with moderate COVID-19. CONCLUSION: Hypokalemia was prevalent in patients with moderate COVID-19 in Yangzhou, China. Hypokalemia was associated with the prolonged hospital stay in patients with moderate COVID-19.

Long noncoding RNA GSEC promotes neutrophil inflammatory activation by supporting PFKFB3-involved glycolytic metabolism in sepsis.

Metabolic reprogramming is a hallmark of neutrophil activation in sepsis. LncRNAs play important roles in manipulating cell metabolism; however, their specific involvement in neutrophil activation in sepsis remains unclear. Here we found that 11 lncRNAs and 105 mRNAs were differentially expressed in three transcriptome datasets (GSE13904, GSE28750, and GSE64457) of gene expression in blood leukocytes and neutrophils of septic patients and healthy volunteers. After Gene Ontology biological process analysis and lncRNA-mRNA pathway network construction, we noticed that GSEC lncRNA and PFKFB3 were co-expressed and associated with enhanced glycolytic metabolism. Our clinical observations confirmed the expression patterns of GSEC lncRNA and PFKFB3 genes in neutrophils in septic patients. Performing in vitro experiments, we found that the expression of GSEC lncRNA and PFKFB3 was increased when neutrophils were treated with inflammatory stimuli. Knockdown and overexpression experiments showed that GSEC lncRNA was essential for mediating PFKFB3 mRNA expression and stability in neutrophil-like dHL-60 cells. In addition, we found that GSEC lncRNA-induced PFKFB3 expression was essential for mediating dHL-60 cell inflammatory cytokine expression. Performing mechanistic experiments, we found that glycolytic metabolism with PFKFB3 involvement supported inflammatory cytokine expression. In summary, our study uncovers a mechanism by which GSEC lncRNA promotes neutrophil inflammatory activation in sepsis by supporting glycolytic metabolism with PFKFB3.

Immune Dysfunction is Associated with Readmission in Survivors of Sepsis Following Infected Pancreatic Necrosis.

OBJECTIVE: Immunosuppression is common in patients with infected pancreatic necrosis (IPN) and associated with morbidity and mortality. This study aimed to investigate the impact of immune status on mortality and readmission after hospital discharge in patients with IPN-related sepsis. METHODS: In this prospective observational study, eligible adult patients with IPN-related sepsis requiring ICU admission were included. Monocytic human leukocyte antigen DR (mHLA-DR), expression of regulatory T cells (Treg), and neutrophil CD88 (nCD88) were measured on the diagnosis of sepsis, ICU discharge, hospital discharge, and 15, 30, 60 days after hospital discharge. Logistic regression model was used to assess potential risk factors for readmission 60-days within the index discharge. RESULTS: A total of 53 patients were included, 13 died during hospitalization and one withdrew the consent soon after discharge. Among the survivors, a tendency of immune recovery was observed during the consecutive follow-ups, evidenced by the increased expression of mHLA-DR. Sixteen patients (41.03%) were readmitted within 60 days after the index discharge. In the multivariable regression model, APACHE II score when sepsis was diagnosed >9 and mHLA-DR at discharged <14,591 AB/C were found to be independent risk factors affecting readmission. CONCLUSION: Immunosuppression is common in patients with IPN-related sepsis and can persist until two months after discharge. The compromised mHLA-DR level at discharge was associated with readmission within two months after discharge.

Trajectories of Lymphocyte Counts in the Early Phase of Acute Pancreatitis Are Associated With Infected Pancreatic Necrosis.

INTRODUCTION: Infected pancreatic necrosis (IPN) is an important complication of acute pancreatitis (AP). Absolute lymphocyte count (ALC) was reported to be associated with immunosuppression and the development of IPN. The aim of this study was to describe the trajectory of ALC during the early phase of AP and assess its association with IPN. METHODS: We retrospectively screened patients with AP admitted to our center between January 2016 and July 2019. The ALC levels for the first 7 days after admission were collected. Group-based trajectory modeling was performed to detect the trajectories. Cox proportional hazards regression model was adopted to identify potential risk factors of IPN. RESULTS: Overall, 292 patients were enrolled for analysis. A triple-group trajectory model was developed, assigning 116 patients to the low-level ALC group, 133 to the medium-level ALC group, and 43 to the high-level ALC group. There was no overall significant difference regarding the incidence of IPN among the 3 groups (P = 0.066). In pairwise comparison, patients in the low-level ALC group had significantly higher incidence of IPN than those in the high-level ALC group (hazard ratio: 3.50; 95% confidence interval: 1.22-10.00, P = 0.020). Length of hospital stay and intensive care unit stay differed significantly among patients with different trajectories (P = 0.042 and 0.033, respectively). DISCUSSION: Despite the fact that the trajectories of ALC is overall insignificant for the development of IPN, patients with persistent low ALC trajectories during the early phase of AP are more likely to develop IPN when compared with patients with high ALC trajectories.

Lacticaseibacillus rhamnosus TR08 alleviated intestinal injury and modulated microbiota dysbiosis in septic mice.

BACKGROUND: Probiotics are widely used in intestinal microbiota imbalance caused by sepsis, however, the protective mechanism is still unclear. This study aimed to explore protective effect of Lacticaseibacillus rhamnosus TR08 on intestinal injury in septic mice. RESULTS: The levels of serum inflammatory factors were reduced significantly in septic mice treated with L. rhamnosus TR08. The levels of sIgA in terminal ileum were significantly higher in probiotic treatment group than sepsis group. Intestinal pathological damage in septic mice improved and the expression of tight junction proteins increased after probiotic treatment. Sequencing of fecal microbiota showed that the abundance and diversity of probiotic treatment group were significantly better than those of sepsis group, and beneficial bacteria increased while some bacteria decreased in the phylum level. CONCLUSION: L. rhamnosus TR08 could improve the integrity of intestinal barrier, enhance the intestinal mucosal immunity in septic mice, and rebalance the intestinal microecosystem.

Identification and Prediction of Novel Clinical Phenotypes for Intensive Care Patients With SARS-CoV-2 Pneumonia: An Observational Cohort Study.

Background: Phenotypes have been identified within heterogeneous disease, such as acute respiratory distress syndrome and sepsis, which are associated with important prognostic and therapeutic implications. The present study sought to assess whether phenotypes can be derived from intensive care patients with coronavirus disease 2019 (COVID-19), to assess the correlation with prognosis, and to develop a parsimonious model for phenotype identification. Methods: Adult patients with COVID-19 from Tongji hospital between January 2020 and March 2020 were included. The consensus k means clustering and latent class analysis (LCA) were applied to identify phenotypes using 26 clinical variables. We then employed machine learning algorithms to select a maximum of five important classifier variables, which were further used to establish a nested logistic regression model for phenotype identification. Results: Both consensus k means clustering and LCA showed that a two-phenotype model was the best fit for the present cohort (N = 504). A total of 182 patients (36.1%) were classified as hyperactive phenotype, who exhibited a higher 28-day mortality and higher rates of organ dysfunction than did those in hypoactive phenotype. The top five variables used to assign phenotypes were neutrophil-to-lymphocyte ratio (NLR), ratio of pulse oxygen saturation to the fractional concentration of oxygen in inspired air (Spo2/Fio2) ratio, lactate dehydrogenase (LDH), tumor necrosis factor α (TNF-α), and urea nitrogen. From the nested logistic models, three-variable (NLR, Spo2/Fio2 ratio, and LDH) and four-variable (three-variable plus TNF-α) models were adjudicated to be the best performing, with the area under the curve of 0.95 [95% confidence interval (CI) = 0.94-0.97] and 0.97 (95% CI = 0.96-0.98), respectively. Conclusion: We identified two phenotypes within COVID-19, with different host responses and outcomes. The phenotypes can be accurately identified with parsimonious classifier models using three or four variables.

Nutritional practice in critically ill COVID-19 patients: A multicenter ambidirectional cohort study in Wuhan and Jingzhou.

BACKGROUND AND OBJECTIVES: The novel coronavirus disease (COVID-19) epidemic is spreading all over the world. With the number of cases increasing rapidly, the epidemiological data on the nutritional practice is scarce. In this study, we aim to describe the clinical characteristics and nutritional practice in a cohort of critically ill COVID-19 patients. METHODS AND STUDY DESIGN: This is a multicenter, ambidirectional cohort study conducted at 11 hospitals in Hubei Province, China. All eligible critical COVID-19 patients in the study hospital intensive care units at 00:00, March 6th, 2020, were included. Data collection was performed via written case report forms. RESULTS: A total of 44 patients were identified and enrolled, of whom eight died during the 28-day outcome follow- up period. The median interval between hospital admission and the study day was 24 (interquartile range, 13- 26) days and 52.2% (23 of 44) of patients were on invasive mechanical ventilation. The median nutrition risk in critically ill (mNUTRIC) score was 3 (interquartile range, 2-5) on the study day. During the enrolment day, 68.2% (30 of 44) of patients received enteral nutrition (EN), while 6.8% (3 of 44) received parenteral nutrition (PN) alone. Nausea and aspiration were uncommon, with a prevalence of 11.4% (5 of 44) and 6.8% (3 of 44), respectively. As for energy delivery, 69.7% (23 of 33) of patients receiving EN and/or PN were achieving their prescribed targets. CONCLUSIONS: The study showed that EN was frequently applied in critical COVID-19 patients. Energy delivery may be suboptimal in this study requiring more attention.

Downregulation of ATP13A2 in midbrain dopaminergic neurons is related to defective autophagy in a mouse model of Parkinson's disease.

Parkinson's disease (PD) is one of the most common diseases of the nervous system characterized by movement disorders arising from loss of midbrain dopaminergic neurons. The relationship between PD and autophagy has received considerable attention. This study aimed to investigate the involvement of the ATP13A2 gene in damage of dopaminergic neurons induced by abnormal autophagy in a MPTP-induced PD mouse model. MPTP was intraperitoneally injected into C57BL mice at 40 mg/kg for 7 days in experimental group. Saline was injected into mice in the control group. After the injection, the mice were tested at different time points for abnormal limb movement by a swimming test. The brain tissue was collected on day 1, 5, and 7 to measure concentration of intracellular calcium. The expression of ATP13A2 was evaluated by real-time PCR. The expression of α-synclein, LC3, LAMP-2, and CaMKK protein was detected by western blot. We found significant motor dysfunction on day 7 in the experimental group, and the expression of α-synclein in the substantia nigra of the midbrain was significantly increased while the expression of ATP13A2 gene was reduced significantly compared with the control group. The concentration of intracellular calcium in the experimental group was significantly higher than in the control group. Autophagy associated proteins LC3-II and LAMP-2 were downregulated and CaMKK protein was upregulated in midbrain tissues of the experimental group compared to control group. In conclusion, our findings suggest that decreased expression of ATP13A2 may lead to defective autophagy and damage to midbrain dopaminergic neurons.

Comparison of pressure-regulated volume control ventilation and pressure control ventilation in patients with abdominal compartment syndrome.

Mechanical ventilation support is commonly required in abdominal compartment syndrome (ACS). In the present study, pressure-regulated volume control ventilation (PRVCV) was compared to pressure control ventilation (PCV) in patients with ACS. The prospective study included 40 patients with ACS who were randomized into the PCV or PRVCV groups and subjected to the different modes of ventilation. After 6 h of ventilation, arterial blood gas, respiratory mechanics and hemodynamics parameters, as well as the intra-abdominal pressure (IAP) and Sequential Organ Failure Assessment (SOFA) scores were calculated. Compared to the PCV mode, mechanical ventilation with PRVCV lead to a significant decrease in the partial pressure of carbon dioxide, the peak inspiratory pressure, the mean inspiratory pressure, the central venous pressure, the heart rate and the extravascular lung water index. In addition, a marked improvement in pH, partial pressure of oxygen, oxygenation index and pulmonary static compliance was noted. However, no significant differences in airway resistance, mean arterial pressure, or IAP and SOFA scores were obtained. In conclusion, the PRVCV mode is better than the PCV mode in ventilation patients with ACS, and should therefore be used as a lung protective strategy. The present study was registered at Chictr.org (no. ChiCTR1800016869).

Adjuvant rhubarb alleviates organs dysfunction and inhibits inflammation in heat stroke.

The aim of the present study was to investigate the effects of adjuvant rhubarb on the recovery of patients with heat stroke. A total of 85 patients with heat stroke were randomly assigned to two treatment groups: One group receiving conventional treatment for heat stroke (conventional group) and one group receiving rhubarb supplement in addition to conventional treatment (rhubarb group). Liver and kidney function parameters, Acute Physiology and Chronic Health Evaluation (APACHE) II scores, plasma interleukin-6 (IL-6), procalcitonin (PCT), C-reactive protein (CRP) levels and venous white blood cell count (WBC) were analyzed. The length of stay in the intensive care units (ICUs) and hospital were recorded. Kaplan-Meier curves were drawn to determine the 30-day survival of the patients. The results indicated that rhubarb supplementation significantly reduced the WBC, as well as CRP, PCT and IL-6 levels at treatment days 3-5. Furthermore, rhubarb intake was observed to limit heat stroke-induced damage to liver and kidney function by decreasing the abnormally high levels of plasma aspartate aminotransferase, alanine aminotransferase and creatinine. Finally, patients in the rhubarb group had shorter ICU and hospital stays as well as a lower APACHE II score than those in the conventional group. However, no significant difference in the 30-day mortality rate was observed between the two groups. In conclusion, rhubarb intake provided a significant benefit for patients with heat stroke by inhibiting systemic inflammation and mitigating liver and kidney injury.

Plasma long noncoding RNA IL-7R as a prognostic biomarker for clinical outcomes in patients with acute respiratory distress syndrome.

BACKGROUND: Long non-coding RNAs (lncRNAs) regulate a variety of genes and biological processes. Lnc-IL7R plays a considerable role in the regulation of inflammation, but its prognostic potential in acute respiratory distress syndrome (ARDS) has not been fully explained. In this study, the role of lnc-IL7R as a potential biomarker in ARDS was examined. OBJECTIVE: Role of lnc-IL7R as potential biomarker in ARDS. METHODS: LncRNA-IL7R was isolated from the plasma of patients with ARDS and healthy controls and clinical indexes were obtained within 24 h after admission. The relative expression of lnc-IL7R was obtained by quantitative real-time PCR. The correlations between lnc-IL7R and continuous variables in ARDS were tested using Spearman's coefficients. RESULTS: A total of 85 ARDS patients and 49 healthy controls were included. Plasma lnc-IL7R was significantly down-regulated in ARDS compared with the levels in healthy control individuals, especially in severe ARDS (P < .01). The area under the curve (AUC) of lnc-IL7R for ARDS diagnosis was 0.87 (sensitivity 75.3%, specificity 93.9%). The lnc-IL7R levels were correlated with the severity of ARDS (ρ = -0.31, P = .0215), oxygenation index (ρ = 0.61, P < .001), APACHE II score (ρ = -0.04, P = .0230), CRP (ρ = -0.26, P = .0148) and WBC (ρ = -0.29, P = .0064). Lnc-IL7R relative value ≥ 0.33 showed the lower 28-day mortality in the patients with ARDS(P < .05).The survivors showed higher lnc-IL7R level and lower APACHE II score, SOFA score and length of mechanical ventilation than in the non-survivors (P = .0109, P < .001, P < .001 and P = .017, respectively). CONCLUSIONS: Lnc-IL7R is a novel biomarker for the diagnosis of ARDS and predicts the severity of ARDS and 28-day mortality in this patients cohort. TRIAL REGISTRATION: The study was registered with the Chinese Clinical Trial Registry (ChiCTR-DOD-16008657).

Rhubarb vs. glycerin enema for treatment of critically ill patients with intra-abdominal hypertension.

Rhubarb has been used as an evacuant for thousands of years. However, recent research has indicated that rhubarb inhibits inflammation and protects organ function. In the current study, the use of rhubarb was investigated in patients with intra-abdominal hypertension (IAH). Specifically, its dual role in attenuating lung and bowel injury by catharsis and inhibiting inflammation was evaluated. Patients in the glycerin group (n=56) received 110 ml of glycerin enema by coloclysis once daily for 7 to 9 days. Patients in the rhubarb group (n=56) were treated with a mixture of 0.3 g/kg body weight rhubarb powder in 100 ml warm water. The Acute Physiology and Chronic Health Evaluation II (APACHE II), Sepsis-Related Organ Failure Assessment (SOFA), intra-abdominal pressure, procalcitonin (PCT), C-reactive protein (CRP), tumor necrosis factor-α (TNF-α) and interleukin (IL)-6 levels were recorded. The duration of mechanical ventilation (MV), respiratory parameters, first day of enteral nutrition (EN), intensive care unit (ICU) hospital stay and 30-day mortality were also recorded. The APACHE II scores were significantly lower in the rhubarb group compared with the glycerin group from day 3 to 9 (P<0.05 at day 3 and 4; P<0.01 at day 5, 7 and 9). The SOFA scores were significantly lower in the rhubarb group compared with the glycerin group from day 5 to 9 (P<0.05). PCT levels were significantly lower from day 4 to 9 (P<0.05) and the CRP level was significantly lower from day 3 to 9 (P<0.05) in the rhubarb group compared with the glycerin group. The TNF-α and IL-6 were significantly lower in the rhubarb group compared with the glycerin group from day 3 to 9 (P<0.05 at day 3 and 4, P<0.01 at day 5, 7 and 9). The positive end-expiratory pressure and peak inspiratory pressure were significantly lower in the rhubarb group compared with the glycerin group at day 3, 5 and 7 (P<0.05 at day 3 and 5, P<0.01 at day 7), while the oxygenation index (P<0.05) and alveolar-arterial partial pressure of oxygen (P<0.05 at day 3 and 5, P<0.01 at day 7) were significantly improved. Significantly shorter durations of MV and ICU hospital stay, and earlier EN, were observed in the rhubarb group compared with the glycerin group (all P<0.05). Rhubarb treatment was indicated to be beneficial in IAH, by inhibiting inflammation and restoring intestinal function.

Effect of ulinastatin combined with thymosin alpha1 on sepsis: A systematic review and meta-analysis of Chinese and Indian patients.

PURPOSE: To assess the effects of urinary trypsin inhibitor (UTI) ulinastatin combined with thymosin alpha1 (Tα1) on sepsis. MATERIALS AND METHODS: The meta-analysis included 8 randomized controlled trials (N=1112 patients) on UTI-based therapy for sepsis published before July 10, 2016. Two investigators independently extracted data and assessed the quality of each study. The short-term mortality rate, duration of mechanical ventilator and vasopressor use, length of intensive care unit stay, Acute Physiology and Chronic Health Evaluation (APACHE) II score, and differences in inflammatory cytokines (interleukin [IL]-6, IL-10, and tumor necrosis factor α) were assessed using statistical software. RESULTS: Treatment of UTI combined with Tα1 (UTI+Tα1) decreased the short-term mortality rate in septic patients by 36%, 35%, and 31% for 28, 60, 90 days, respectively. UTI+Tα1 decreased the duration of mechanical ventilation and vasopressor use, APACHE II score, and levels of IL-6 and tumor necrosis factor α. Treatment of UTI+Tα1 did not reduce the duration of vasopressor use and length of intensive care unit stay, or increase IL-10 levels. Because of the high heterogeneity of the included trials, the results should be carefully assessed. CONCLUSIONS: Treatment of UTI+Tα1 can suppress the production of proinflammatory cytokines, decrease the APACHE II score, shorten the duration of mechanical ventilation and vasopressor use, and improve the 28-day survival rate.

Effect of ulinastatin combined with thymosin alpha1 on sepsis: A systematic review and meta-analysis of Chinese and Indian patients.

PURPOSE: To assess the effects of urinary trypsin inhibitor (UTI) ulinastatin combined with thymosin alpha1 (Tα1) on sepsis. MATERIALS AND METHODS: The meta-analysis included 8 randomized controlled trials (N=1112 patients) on UTI-based therapy for sepsis published before July 10, 2016. Two investigators independently extracted data and assessed the quality of each study. The short-term mortality rate, duration of mechanical ventilator and vasopressor use, length of intensive care unit stay, Acute Physiology and Chronic Health Evaluation (APACHE) II score, and differences in inflammatory cytokines (interleukin [IL]-6, IL-10, and tumor necrosis factor α) were assessed using statistical software. RESULTS: Treatment of UTI combined with Tα1 (UTI+Tα1) decreased the short-term mortality rate in septic patients by 36%, 35%, and 31% for 28, 60, 90 days, respectively. UTI+Tα1 decreased the duration of mechanical ventilation, APACHE II score, and levels of IL-6 and tumor necrosis factor α. Treatment of UTI+Tα1 did not reduce the duration of vasopressor use and length of intensive care unit stay, or increase IL-10 levels. Because of the high heterogeneity of the included trials, the results should be carefully assessed. CONCLUSIONS: Treatment of UTI+Tα1 can suppress the production of proinflammatory cytokines, decrease the APACHE II score, shorten the duration of mechanical ventilation, and improve the 28-day survival rate.

Emodin alleviates jejunum injury in rats with sepsis by inhibiting inflammation response.

Emodin is an anthraquinone derived from Chinese herb that exerts anti-inflammation effects. This study aimed to investigate whether emodin provides the protection for jejunum injury by inhibiting inflammation. We established a model of sepsis caused by cecal ligation and puncture. Forty-eight male Wistar rats were divided into four groups (n=12). Jejunum injury was assessed by pathological examination. The activity of pJAK1/pSTAT3 and protein levels of Bcl-2 and Bax were detected by Western blot analysis. Inflammatory factors IL-6, TNF-α and procalcitonin were detected by ELISA. Apoptosis was detected by TUNEL. We found that emodin alleviated jejunum damage and apoptosis induced by sepsis and decreased the levels of IL-6, TNF-α and procalcitonin in septic rats. Furthermore, we observed that emodin increased the levels of pJAK1 and of pSTAT3, which were decreased in rats with sepsis. In addition, emodin enhanced the expression of Bcl-2 which was downregulated by sepsis and decreased the expression of Bax which was upregulated by sepsis. In conclusion, these results indicate that emodin suppresses inflammatory response induced by sepsis. Emodin activates JAK1/STAT3 signaling pathway and regulates Bcl-2 and Bax expression to protect the jejunum in rats with sepsis.

Emodin alleviates lung injury in rats with sepsis.

BACKGROUND: Sepsis has high morbidity and mortality. The aim of this study was to investigate whether emodin, an anthraquinone derived from Chinese herb, exerts protective effects on lung injury in rat model of sepsis. MATERIALS AND METHODS: Forty-eight male Wistar rats were randomly divided into four groups (n = 12): normal group, sham-operated group, cecal ligation and puncture (CLP) model group, and emodin-treated group. Saline or emodin (25 mg/kg) was injected intraperitoneally 0.5 h before CLP. The rats were sacrificed 48 h after CLP. Lung wet-to-dry weight ratio and pathologic changes in the lung were examined, the contents of malondialdehyde and myeloperoxidase in lung tissue were detected, serum tumor necrosis factor alpha and interleukin 6 levels were measured by enzyme-linked immunosorbent assay, and the phosphorylation of p38 mitogen-activated protein kinase (p38 MAPK) was detected by Western blot analysis. RESULTS: Compared with control group, CLP group exhibited higher wet-to-dry weight ratio and water content in the lung (P < 0.01), but these indexes were reduced and pathologic changes in the lung were relieved in the emodin-treated group. In addition, lung malondialdehyde and myeloperoxidase contents, serum levels of tumor necrosis factor alpha and interleukin 6, and phosphorylation of p38 MAPK increased in the CLP group but decreased in the emodin-treated group (P < 0.05). CONCLUSIONS: Emodin exerts protective effects on lung injury in septic rats, which is related to the inhibition of p38 MAPK pathway and the reduction of oxidative stress and inflammation response during sepsis.

Low-molecular-weight heparin and intermittent pneumatic compression for thromboprophylaxis in critical patients.

The efficacy and safety of physiotherapeutic prophylaxis for venous thromboembolism in critically ill patients with heparin contraindication remains unclear. In the present study it was hypothesized that physiotherapy prophylaxis with intermittent pneumatic compression (IPC) would be safe and effective for patients unable to receive low-molecular-weight heparin (LMWH). In addition, this study investigated whether a combined therapy of IPC with LMWH would be more effective for the prophylaxis of deep vein thrombosis (DVT) in critical patients. A total of 500 patients were divided into four groups according to the prophylaxis of DVT. The IPC group consisted of 95 patients with heparin contraindication that received IPC treatment; the LMWH group consisted of 185 patients that received an LMWH injection; the LMWH + IPC group consisted of 75 patients that received IPC treatment and LMWH injection; and the control group consisted of 145 patients that received no IPC treatment or injection of LMWH. Each patient was evaluated clinically for development of DVT and the diagnosis was confirmed by Doppler study. Venous thromboembolism was a common complication among the trauma patients with severe injuries. Patients responded positively to the treatment used in the intervention groups. Patients exhibited an improved response to LMWH + ICP compared with IPC or LMWH alone, while no significant difference was detected between the IPC and LMWH groups. These results were applicable to patients that had a Wells score of ≥3; however, no significant differences in DVT incidence were observed among the patients who had a Wells score of <3. In this observational study, LMWH + ICP appeared to be more effective than either treatment alone in treating critically ill trauma patients with severe injuries that are at high risk for VTE and bleeding simultaneously.

Recombinant human interleukin-11 (IL-11) is a protective factor in severe sepsis with thrombocytopenia: A case-control study.

OBJECTIVE: To examine the platelet recovering and anti-inflammatory effects of IL-11 in the treatment of sepsis, accompanied with thrombocytopenia and to investigate the associated mechanisms via a case-control study. METHODS: 105 patients enrolled for the study were segregated into (1) IL-11 therapy group and (2) conventional therapy group. The IL-11 therapy group was given additional recombinant human IL-11 treatment. Laboratory examinations of IL-11, IL-6, TNF-α, PT, APTT, WBC, PLT counts in blood routine assays and PCT, CRP and APACHE II scores were performed and the results were recorded. RESULTS: The PLT counts in the IL-11 therapy group were higher than those in the conventional therapy group. No obvious difference in WBC counts or CRP levels was observed between the two groups. The highest levels of TNF-α were observed on day 3 in the conventional therapy group while it was observed on day 1 in the IL-11 therapy group, both of which subsequently declined gradually. The level of IL-6 was significantly lower in the IL-11 therapy group from 3 to 14 days, while there was a gradual elevation of IL-11. IL-11 therapy downregulated the expression of the sepsis indicator PCT and reduced the APACHE II score from 3 to 14 days. The conventional therapy group had a significantly higher mortality rate within 28 days. CONCLUSION: IL-11 has a protective role and can accelerate recovery of platelets, and remarkably lessen the extent of inflammatory responses, hence reducing the mortality in sepsis patients accompanied with thrombocytopenia.