The expression of CD86 in CD3+CD56+ NKT cells is associated with the occurrence and prognosis of sepsis-associated encephalopathy in sepsis patients: a prospective observational cohort study.

The role of CD3+CD56+ natural killer T (NKT) cells and its co-signaling molecules in patients with sepsis-associated encephalopathy (SAE) is unknown. In this prospective observational cohort study, we initially recruited 260 septic patients and eventually analyzed 90 patients, of whom 57 were in the SAE group and 37 were in the non-SAE group. Compared to the non-SAE group, 28-day mortality was significantly increased in the SAE group (33.3% vs. 12.1%, p = 0.026), while the mean fluorescence intensity (MFI) of CD86 in CD3+CD56+ NKT cells was significantly lower (2065.8 (1625.5 ~ 3198.8) vs. 3117.8 (2278.1 ~ 5349), p = 0.007). Multivariate analysis showed that MFI of CD86 in NKT cells, APACHE II score, and serum albumin were independent risk factors for SAE. Furthermore, the Kaplan-Meier survival analysis indicated that the mortality rate was significantly higher in the high-risk group than in the low-risk group (χ2 = 14.779, p < 0.001). This study showed that the decreased expression of CD86 in CD3+CD56+ NKT cells is an independent risk factor of SAE; thus, a prediction model including MFI of CD86 in NKT cells, APACHE II score, and serum albumin can be constructed for diagnosing SAE and predicting prognosis.

Comparison of clinical characteristics in patients with coronavirus disease and influenza A in Guangzhou, China.

BACKGROUND: This study aims to compare the epidemiological, clinical and laboratory characteristics between patients with coronavirus disease (COVID-19) and influenza A (H1N1), and to develop a differentiating model and a simple scoring system. METHODS: We retrospectively analyzed the data from patients with COVID-19 and H1N1. The logistic regression model based on clinical and laboratory characteristics was constructed to distinguish COVID-19 from H1N1. Scores were assigned to each of independent discrimination factors based on their odds ratios. The performance of the prediction model and scoring system was assessed. RESULTS: A total of 236 patients were recruited, including 20 COVID-19 patients and 216 H1N1 patients. Logistic regression revealed that age >34 years, temperature ≤37.5 °C, no sputum or myalgia, lymphocyte ratio ≥20% and creatine kinase-myocardial band isoenzyme (CK-MB) >9.7 U/L were independent differentiating factors for COVID-19. The area under curves (AUCs) of the prediction model and scoring system in differentiating COVID-19 from H1N1 were 0.988 and 0.962, respectively. CONCLUSIONS: There are certain differences in clinical and laboratory features between patients with COVID-19 and H1N1. The simple scoring system may be a useful tool for the early identification of COVID-19 patients from H1N1 patients.

Effects of dexmedetomidine on heart rate control and pre-operative outcome in patients with acute aortic dissection: a propensity-matched analysis.

BACKGROUND: The total survival rate in patients with acute aortic dissection (AAD) has been greatly improved because of surgical technique advances. However, the pre-operative mortality rate remained high. In this study, we sought to evaluate the effects of dexmedetomidine (DEX) on heart rate control and preoperative outcome in AAD. METHODS: Retrospectively enrolled 461 patients who were diagnosed with AAD during the first 7-day after admission and divided into two groups according to the use of intravenous DEX: DEX group (91 patients) and Control group (370 patients). The heart rate and systolic blood pressure (SBP) level in both groups were recorded, and the incidence of aortic dissection rupture and pre-operative survival rates within 7 days were considered as the primary clinical outcomes. RESULTS: Compared to the Control group, heart rate of DEX group in the early 3 hours was significantly higher (P=0.009), and the 24-hour heart rate fluctuation was smaller (P=0.012). There was no difference in the systolic blood pressure (SBP) between the two groups, but the 24-hour fluctuation of SBP in DEX group was less (P=0.003). We performed a propensity-matched analysis to minimize selection bias and found that there were 7 (7.9%) patients in the DEX group occurred acute pulmonary edema, 17 (19.1%) patients in the Control group (P=0.047). And the pre-operative survival rates within 7 days were significantly improved in DEX group (P=0.004). And the pre-operative survival rates within 7 days were significantly improved in DEX group (P=0.004). CONCLUSIONS: DEX can be beneficial to facilitate heart rate control, keep SBP more steady, and reduce the incidence of pre-operative aortic rupture in patients with AAD.

Hypercapnia promotes microglial pyroptosis via inhibiting mitophagy in hypoxemic adult rats.

BACKGROUND: Hypoxemia is a typical symptom of acute respiratory distress syndrome. To avoid pulmonary morbidity, low tidal volume ventilation is often applied. The ventilation strategy will certainly cause hypercapnia. This study aimed to explore whether hypercapnia would promote microglial pyroptosis via inhibiting mitophagy in adult rats with hypoxemia. METHODS: The cerebral oxygen extraction ratio (CERO2 ) and partial pressure of brain tissue oxygen (PbtO2 ) in a rat model of hypercapnia/hypoxemia were assessed. The reactive oxygen species (ROS) production and the expression of LC3-II/I, p62, caspase-1, gasdermin D-N domains (GSDMD-N), IL-1ß, and IL-18 in microglial cells were detected. RESULTS: Hypercapnia decreased the PbtO2 levels of the hypoxic rats, which was further evidenced by the increased levels of CERO2 . Expression levels of LC3-II were reduced, while p62 expression was increased by hypercapnia in hypoxic microglia. Hypercapnia increased the production of ROS and the expression of caspase-1, GSDMD-N, IL-1ß, and IL-18 in hypoxia-activated microglia. Scavenging ROS inhibited microglial pyroptosis and expression of IL-1ß and IL-18. CONCLUSIONS: These results suggest that hypercapnia-induced mitophagy inhibition may promote pyroptosis and enhance IL-1ß and IL-18 release in hypoxia-activated microglia.

Hypertonic saline mediates the NLRP3/IL-1ß signaling axis in microglia to alleviate ischemic blood-brain barrier permeability by downregulating astrocyte-derived VEGF in rats.

INTRODUCTION: The aim of this study was to explore whether the antibrain edema of hypertonic saline (HS) is associated with alleviating ischemic blood-brain barrier (BBB) permeability by downregulating astrocyte-derived vascular endothelial growth factor (VEGF), which is mediated by microglia-derived NOD-like receptor protein 3 (NLRP3) inflammasome. METHODS: The infarct volume and BBB permeability were detected. The protein expression level of VEGF in astrocytes in a transient focal brain ischemia model of rats was evaluated after 10% HS treatment. Changes in the NLRP3 inflammasome, IL-1ß protein expression, and the interleukin-1 receptor (IL1R1)/pNF-кBp65/VEGF signaling pathway were determined in astrocytes. RESULTS: HS alleviated the BBB permeability, reduced the infarct volume, and downregulated the expression of VEGF in astrocytes. HS downregulates IL-1ß expression by inhibiting the activation of the NLRP3 inflammasome in microglia and then downregulates VEGF expression by inhibiting the phosphorylation of NF-кBp65 mediated by IL-1ß in astrocytes. CONCLUSIONS: HS alleviated the BBB permeability, reduced the infarct volume, and downregulated the expression of VEGF in astrocytes. HS downregulated IL-1ß expression via inhibiting the activation of the NLRP3 inflammasome in microglia and then downregulated VEGF expression through inhibiting the phosphorylation of NF-кBp65 mediated by IL-1ß in astrocytes.

Presepsin level in predicting patients' in-hospital mortality from sepsis under sepsis-3 criteria.

Background: Early recognition of septic patients with poor prognosis is important for clinicians to prescribe personalized therapies which include timely fluid resuscitation therapy and appropriate antimicrobial therapy. We aimed to evaluate the effect of the presepsin level on predicting the prognosis of patients with sepsis under the sepsis-3 criteria. Methods: Patients who were diagnosed as sepsis under the sepsis-3 criteria were recruited and assigned to the survivor group and the non-survivor group according to their in-hospital mortality. The two groups' baseline characteristics were analyzed with Pearson's chi-square (χ 2) test or Kruskal-Wallis test. Binary logistic regression analysis was performed to determine the independent predictors of in-hospital mortality from sepsis. Receiver operating characteristic analysis was conducted to evaluate the efficacy of presepsin in predicting patients' in-hospital mortality from sepsis. The correlation between presepsin and the Sequential Organ Failure Assessment (SOFA) score was measured with Spearman's rank correlation coefficient. P-values of less than 0.05 were considered to indicate statistical significance. Results: Overall, 138 patients were included in this study. The presepsin level of the non-survivor group was significantly higher than that of the other group (P=0.000). Binary logistic regression showed that the presepsin level was an independent risk factor of patients' in-hospital mortality from sepsis (OR =1.221 P=0.026). The presepsin level was positively associated with the SOFA score (ρ=0.396, P=0.000). ROC curve analysis revealed the presepsin level was highly accurate in predicting patients' in-hospital mortality from sepsis (AUC =0.703, P=0.000). The AUC value of a combination of presepsin and the SOFA score was significantly larger than that of the SOFA score alone (AUC: 0.817 vs 0.793, P=0.041). Conclusions: Presepsin is a prognostic biomarker with high accuracy in predicting the prognosis of sepsis under the sepsis-3 criteria.

Ulinastatin Ameliorates Pulmonary Capillary Endothelial Permeability Induced by Sepsis Through Protection of Tight Junctions via Inhibition of TNF-α and Related Pathways.

Background: Increased permeability of pulmonary capillary is a common consequence of sepsis that leads to acute lung injury. In this connection, ulinastatin, a urinary trypsin inhibitor (UTI), is used clinically to mitigate pulmonary edema caused by sepsis. However, the underlying mechanism of UTI in alleviating sepsis-associated pulmonary edema remains to be fully elucidated. As tight junctions (TJs) between the pulmonary microvascular endothelial cells (PMVECs) play a pivotal role in the permeability of pulmonary capillary, this study investigated the effect of UTI on expression of junctional proteins in PMVECs during sepsis. Methods: Male adult Sprague Dawley rats were subjected to cecal ligation and puncture (CLP) and divided into sham, CLP, and UTI+CLP groups. UTI was administered every 8 h for 3 days before CLP. At 48 h after surgery, Evans blue (EB) was administered to evaluate the pulmonary vascular leakage. Histological staining was used for evaluation of lung injury score. Using immunofluorescence staining and Western blot, the expression of junctional proteins (occludin, claudin-5, and ZO-1) in pulmonary endothelia was assessed. In vitro, PMVECs were divided into control, lipopolysaccharide (LPS), and UTI+LPS groups for examination of expression of junctional proteins and TNF-α as well as inhibitor of NF-κB (IκB), p38 mitogen-activated protein kinases (p38 MAPKs), c-Jun N-terminal kinases (JNKs), and extracellular signal-regulated kinases (ERKs) signaling pathways. Additionally, the expression of various junctional proteins was determined in PMVECs of control, LPS, and TNF-α receptor antagonist-LPS groups. PMVECs were also treated with TNF-α and TNF-α receptor antagonist and the expression of various junctional proteins was assessed. Results: Compared with the CLP group, UTI markedly decreased EB leakage and lung injury score. The expression of occludin, claudin-5, and ZO-1 was decreased in both CLP rats and LPS-treated PMVECs, but it was reversed by UTI and TNF-α receptor antagonist. TNF-α expression was vigorously elevated in the lung of CLP rats and in LPS-challenged PMVECs, which were suppressed by UTI. In addition, TNF-α also reduced occludin, claudin-5, and ZO-1 expression in PMVECs, but these effects of TNF-α were antagonized by pretreatment with TNF-α receptor antagonist. Furthermore, UTI inhibited LPS-induced activation of NF-κB and mitogen-activated protein kinases (MAPKs) pathways in PMVECs. Conclusion: UTI effectively protects TJs and helps to attenuate the permeability of pulmonary capillary endothelial cells during sepsis through inhibiting NF-κB and MAPKs signal pathways and TNF-α expression.

Hypercapnia induces IL-1ß overproduction via activation of NLRP3 inflammasome: implication in cognitive impairment in hypoxemic adult rats.

BACKGROUND: Cognitive impairment is one of common complications of acute respiratory distress syndrome (ARDS). Increasing evidence suggests that interleukin-1 beta (IL-1ß) plays a role in inducing neuronal apoptosis in cognitive dysfunction. The lung protective ventilatory strategies, which serve to reduce pulmonary morbidity for ARDS patients, almost always lead to hypercapnia. Some studies have reported that hypercapnia contributes to the risk of cognitive impairment and IL-1ß secretion outside the central nervous system (CNS). However, the underlying mechanism of hypercapnia aggravating cognitive impairment under hypoxia has remained uncertain. This study was aimed to explore whether hypercapnia would partake in increasing IL-1ß secretion via activating the NLRP3 (NLR family, pyrin domain-containing 3) inflammasome in the hypoxic CNS and in aggravating cognitive impairment. METHODS: The Sprague-Dawley (SD) rats that underwent hypercapnia/hypoxemia were used for assessment of NLRP3, caspase-1, IL-1ß, Bcl-2, Bax, and caspase-3 expression by Western blotting or double immunofluorescence, and the model was also used for Morris water maze test. In addition, Z-YVAD-FMK, a caspase-1 inhibitor, was used to treat BV-2 microglia to determine whether activation of NLRP3 inflammasome was required for the enhancing effect of hypercapnia on expressing IL-1ß by Western blotting or double immunofluorescence. The interaction effects were analyzed by factorial ANOVA. Simple effects analyses were performed when an interaction was observed. RESULTS: There were interaction effects on cognitive impairment, apoptosis of hippocampal neurons, activation of NLRP3 inflammasome, and upregulation of IL-1ß between hypercapnia treatment and hypoxia treatment. Hypercapnia + hypoxia treatment caused more serious damage to the learning and memory of rats than those subjected to hypoxia treatment alone. Expression levels of Bcl-2 were reduced, while that of Bax and caspase-3 were increased by hypercapnia in hypoxic hippocampus. Hypercapnia markedly increased the expression of NLRP3, caspase-1, and IL-1ß in hypoxia-activated microglia both in vivo and in vitro. Pharmacological inhibition of NLRP3 inflammasome activation and release of IL-1ß might ameliorate apoptosis of neurons. CONCLUSIONS: The present results suggest that hypercapnia-induced IL-1ß overproduction via activating the NLRP3 inflammasome by hypoxia-activated microglia may augment neuroinflammation, increase neuronal cell death, and contribute to the pathogenesis of cognitive impairments.

Hypertonic saline attenuates expression of Notch signaling and proinflammatory mediators in activated microglia in experimentally induced cerebral ischemia and hypoxic BV-2 microglia.

BACKGROUND: Ischemic stroke is a major disease that threatens human health in ageing population. Increasing evidence has shown that neuroinflammatory mediators play crucial roles in the pathophysiology of cerebral ischemia injury. Notch signaling is recognized as the cell fate signaling but recent evidence indicates that it may be involved in the inflammatory response in activated microglia in cerebral ischemia. Previous report in our group demonstrated hypertonic saline (HS) could reduce the release of interleukin-1 beta and tumor necrosis factor-alpha in activated microglia, but the underlying molecular and cellular mechanisms have remained uncertain. This study was aimed to explore whether HS would partake in regulating production of proinflammatory mediators through Notch signaling. RESULTS: HS markedly attenuated the expression of Notch-1, NICD, RBP-JK and Hes-1 in activated microglia both in vivo and in vitro. Remarkably, HS also reduced the expression of iNOS in vivo, while the in vitro levels of inflammatory mediators Phos-NF-κB, iNOS and ROS were reduced by HS as well. CONCLUSION: Our results suggest that HS may suppress of inflammatory mediators following ischemia/hypoxic through the Notch signaling which operates synergistically with NF-κB pathway in activated microglia. Our study has provided the morphological and biochemical evidence that HS can attenuate inflammation reaction and can be neuroprotective in cerebral ischemia, thus supporting the use of hypertonic saline by clinicians in patients with an ischemia stroke.

Hypertonic saline protects brain endothelial cells against hypoxia correlated to the levels of epidermal growth factor receptor and interleukin-1ß.

OBJECTIVE: The aim of this study was to verify the protective effect of hypertonic saline (HS) on brain endothelial cells under hypoxic conditions and the relevant underlying mechanism. METHODS: bEnd.3 cells were treated with oxygen-glucose deprivation (OGD)-induced injury. To measure HS performance, cell viability was determined using the 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium salt assay, and cell apoptosis was assessed by flow cytometry and Terminal deoxynucleotidyl transferase UTP nick-end labeling staining. RNA-seq was performed to assess the expression profiles and screen the candidate genes that participated in OGD-induced injury and the HS protective effect. Quantitative real-time polymerase chain reaction (qPCR) and western blot analysis were used to confirm the expression of candidate genes, and enzyme-linked immunosorbent assay was used to measure the level of interleukin (IL)-1ß. Overexpression analyses were performed to confirm the functions of the differentially expressed genes. RESULTS: HS with a concentration of 40 mmol/L NaCl had an obvious protective effect on bEnd.3 cells after OGD-induced injury, resulting in increased cell viability and a smaller percentage of apoptotic cells. According to the RNA-seq results, epidermal growth factor receptor (EGFR) was chosen as the differentially expressed gene target in this study. The qPCR and western blot analyses further confirmed that the levels of EGFR/phosphorylated epidermal growth factor receptor and IL-1ß were enhanced after OGD-induced injury, but attenuated after treatment with 40 mmol/L of NaCl HS. Overexpressed EGFR reversed the protective effect of HS that caused low viability and high rates of apoptosis in cells. CONCLUSION: HS can protect endothelial cells against OGD-induced injury, but is affected by the expression of EGFR/p-EGFR and IL-1ß.

Rapamycin inhibits lipopolysaccharide-induced neuroinflammation in vitro and in vivo.

Alzheimer's disease (AD) is the most common type of progressive neurodegenerative disorder, and is responsible for the most common form of dementia in the elderly. Inflammation occurs in the brains of patients with AD, and is critical for disease progression. In the present study, the effects of rapamycin (RAPA) on neuroinflammation lipopolysaccharide (LPS)-induced were investigated. SH­SY5Y human neuroblastoma cells were treated with 20 µg/ml LPS and 0.1, 1 or 10 nmol/l RAPA, and were analyzed at various time points (6, 12 and 24 h). The mRNA expression levels of interleukin (IL) 1ß, IL6 and hypoxia­inducible factor 1α (HIF1α) were determined using reverse transcription­quantitative polymerase chain reaction. The protein expression levels of phosphorylated (p­)S6, p­nuclear factor κB (NFκB), p­inhibitor of NFκB kinase subunit ß (IKKß) and p­tau protein were measured by western blot analysis. p­IKKß, p­NFκB, p­S6 and p­tau were significantly decreased at 6, 12 and 24 h when cells were treated with ≥0.1 nmol/ml RAPA. In addition, female Sprague Dawley rats were intracranially injected with a single dose of 100 µg/kg LPS in the absence or presence of 1 mg/kg RAPA pretreatment. Brain tissues were subjected to immunohistochemical analysis 6­24 h later, which revealed that the expression levels of HIF1α and p­S6 in rat cerebral cortex were increased following LPS injection; however, this increase was abrogated by RAPA treatment. RAPA may therefore be considered a potential therapeutic agent for the early or emergency treatment of neuroinflammation.

Huperzine A protects sepsis associated encephalopathy by promoting the deficient cholinergic nervous function.

Neuroinflammatory deregulation in the brain plays a crucial role in the pathogenesis of sepsis associated encephalopathy (SAE). Given the mounting evidence of anti-inflammatory and neuroprotective effects of the cholinergic nervous system, it is surprising that there is little information about its changes in the brain during sepsis. To elucidate the role of the cholinergic nervous system in SAE, hippocampal choline acetyltransferase, muscarinic acetylcholine receptor-1, acetylcholinesterase and acetylcholine were evaluated in LPS-induced sepsis rats. Expression of pro-inflammatory cytokines, neuronal apoptosis, and animal cognitive performance were also assessed. Furthermore, therapeutic effects of the acetylcholinesterase inhibitor Huperzine A (HupA) on the hippocampal cholinergic nervous function and neuroinflammation were evaluated. A deficiency of the cholinergic nervous function was revealed in SAE, accompanied with over-expressed pro-inflammatory cytokines, increase in neuronal apoptosis and brain cognitive impairment. HupA remarkably promoted the deficient cholinergic nervous function and attenuated the abnormal neuroinflammation in SAE, paralleled with the recovery of brain function. We suggest that the deficiency of the cholinergic nervous function and the abnormal neuroinflammation are synergistically implicated in the pathogenesis of SAE. Thus, HupA is a potential therapeutic candidate for SAE, as it improves the deficient cholinergic nervous function and exerts anti-inflammatory action.

Hypertonic saline alleviates cerebral edema by inhibiting microglia-derived TNF-α and IL-1ß-induced Na-K-Cl Cotransporter up-regulation.

BACKGROUND: Hypertonic saline (HS) has been successfully used clinically for treatment of various forms of cerebral edema. Up-regulated expression of Na-K-Cl Cotransporter 1 (NKCC1) and inflammatory mediators such as tumor necrosis factor alpha (TNF-α) and interleukin-1 beta (IL-1ß) has been demonstrated to be closely associated with the pathogenesis of cerebral edema resulting from a variety of brain injuries. This study aimed to explore if alleviation of cerebral edema by 10% HS might be effected through down-regulation of inflammatory mediator expression in the microglia, and thus result in decreased NKCC1 expression in astrocytes in the cerebral cortex bordering the ischemic core. METHODS: The Sprague-Dawley (SD) rats that underwent right-sided middle cerebral artery occlusion (MCAO) were used for assessment of NKCC1, TNF-α and IL-1ß expression using Western blotting, double immunofluorescence and real time RT-PCR, and the model also was used for evaluation of brain water content (BWC) and infarct size. SB203580 and SP600125, specific inhibitors of the p38 and JNK signaling pathways, were used to treat primary microglia cultures to determine whether the two signaling pathways were required for the inhibition of HS on microglia expressing and secreting TNF-α and IL-1ß using Western blotting, double immunofluorescence and enzyme-linked immunosorbent assay (ELISA). The effect of TNF-α and IL-1ß on NKCC1 expression in primary astrocyte cultures was determined. In addition, the direct inhibitory effect of HS on NKCC1 expression in primary astrocytes was also investigated by Western blotting, double immunofluorescence and real time RT-PCR. RESULTS: BWC and infarct size decreased significantly after 10% HS treatment. TNF-α and IL-1ß immunoexpression in microglia was noticeably decreased. Concomitantly, NKCC1 expression in astrocytes was down-regulated. TNF-α and IL-1ß released from the primary microglia subjected to hypoxic exposure and treatment with 100 mM HS were decreased. NKCC1 expression in primary astrocytes was concurrently and progressively down-regulated with decreasing concentration of exogenous TNF-α and IL-1ß. Additionally, 100 mM HS directly inhibited NKCC1 up-regulation in astrocytes under hypoxic condition. CONCLUSIONS: The results suggest that 10% HS alleviates cerebral edema through inhibition of the NKCC1 Cotransporter, which is mediated by attenuation of TNF-α and IL-1ß stimulation on NKCC1.

[Procalcitonin change pattern in patients with septic shock and its relationship with prognosis].

OBJECTIVE: To investigate procalcitonin (PCT) change pattern in patients with septic shock and its relationship with prognosis. METHODS: Sixty-three septic shock patients were enrolled, and levels of PCT, C-reactive protein (CRP) as well as white blood cell (WBC) on 1st, 3rd, 5th,7th day after admission to intensive care unit (ICU) were checked. Patients were divided into survival group and death group according to 28-day survival result. Differences in parameters between two groups were compared. The change regulation of parameters along with in-hospital period and its relationship with prognosis were analyzed by multilevel linear model. RESULTS: There were 41 patients in survival group and 22 patients in death group. PCT and CRP level decreased in survival group with time dependency pattern, while death group increased. The PCT at 3, 5, 7 days after admission to ICU in death group were significantly higher than those in survivors (3 days: 8.7±3.7 µg/L vs. 5.6±1.7 µg/L, 5 days: 10.3±1.3 µg/L vs. 4.8±2.3 µg/L, 7 days: 12.7±2.3 µg/L vs. 0.8±0.3 µg/L, P<0.05 or P<0.01), and CRP at 5 days and 7 days was significantly higher than those in survival group (5 days: 447±63 mg/L vs. 355±91 mg/L, 7 days: 439±45 mg/L vs. 364±63 mg/L, both P<0.05). Two groups of WBC did not change significantly, and there were no statistical significance difference at each time point between the two groups. What's more, the effect analysis results showed that there were significant changes in PCT as ICU day prolonged (F=10.91, P= 0.00), and there was a significant difference between the survivor and the dead (F=7.58, P=0.00), while CRP changed only with ICU stays (F=4.17, P=0.03). CONCLUSIONS: Compared with CRP and WBC, PCT had higher sensitivity in predicting prognosis, sustainable elevation of PCT level indicates poor prognosis, serum PCT can be used as one of indexes predicting prognosis of septic shock.

[Distribution and antibiotic resistance of bacteria causing bloodstream infections in patients in intensive care unit].

OBJECTIVE: To investigate the distribution and antibiotic resistance of bacteria causing bloodstream infections in intensive care unit (ICU) patients and to provide a basis for rational clinical use of antibiotics. METHODS: The data of positive specimens, including whole blood, catheter blood and bone marrow samples, were isolated from ICU patients from January 2010 to December 2012. Disc diffusion method, micro-dilution and Etest method were used to test drug sensitivity. Distribution and antibiotic resistance of bacteria were analyzed retrospectively. RESULTS: A total of 1077 strains were isolated from 903 patients with bloodstream infection during 3 years. Gram-positive (G⁺) bacteria and Gram-negative (G⁻) bacteria accounted for 59.33% (639 isolates) and 40.67% (438 isolates) respectively. The 5 most frequently isolated bacteria were Staphylococcus epidermidis (20.06%, 216 isolates) followed in order by Escherichia coli (13.93%, 150 isolates), Acinetobacter baumannii (10.03%, 108 isolates), Klebsiella pneumonia (7.80%, 84 isolates) and Staphylococcus aureus (6.96%, 75 isolates). There was no significant difference in distribution of bacteria during 3 years. The resistance rate of Staphylococcus epidermidis was higher than that of Staphylococcus aureus to most of the tested drugs. The resistance rate of Staphylococcus epidermidis to quinoline/dalfopristin (4.2%) and nitrofurazone (15.3%) was relatively low, while resistance to penicillin (94.4%), linezolid (93.1%), piperacillin/tazobactam (90.3%), cefoperazone/sulbactam (87.5%) and oxacillin (83.3%) was over 80%. The resistance rate of Staphylococcus aureus to penicillin (96.0%), cefoperazone/sulbactam (84.0%), linezolid (76.0%) and oxacillin (76.0%) was over 70%, and resistance to the other common antibacterial drugs was below 70%. The resistance rate of Acinetobacter baumannii to amikacin (38.9%), nitrofurazone (91.7%), cefotetan (88.9%), ceftazidime (88.9%), ampicillin (88.9%), ceftriaxone (86.1%), the cefepime (86.1%), aztreonam (80.6%) and cefazolin (80.6%), and overall above 80%. The resistance rate of Escherichia coli to amikacin (30.0%), cefotetan (24.0%) and imipenem (16.0%) was below 30%, while resistance to ampicillin/sulbactam (94.0%), levofloxacin (84.0%), ampicillin (84.0%) and ceftriaxone (80.0%) was over 80%. CONCLUSIONS: Among the bacteria causing bloodstream infection as isolated from ICU patients, G(+) and G(-) bacteria accounted for 59.33% and 40.67%, respectively. The resistance rate of G(-) was higher than that of G(+), and resistance rate of majority of bacteria was higher than 60% on average. Before obtaining the susceptibility test Results, both G(-) and G(+) should be taken into account on choosing antimicrobial drugs in the treatment of ICU patients.

[Clinical value of extravascular lung water and preload parameters in weaning of mechanical ventilation in patients with septic shock].

OBJECTIVE: To investigate the values of extravascular lung water and preload parameters of weaning from mechanical ventilation on patients with septic shock. METHODS: A prospective study was conducted. A total of 52 septic shock patients with mechanical ventilation were enrolled from January 2010 to July 2012. All patients were treated and monitored by pulse induced continuous cardiac output (PiCCO) till they reached weaning criteria, and then spontaneous breathing trial (SBT), weaning, and extubation were performed in turn. The enrolled patients were divided into two groups including successful weaning group (n=38) and weaning failure group (n=14) according to clinical manifestations during 48 hours after weaning. Extravascular lung water index (EVLWI), preload parameters such as global end diastolic volume index (GEDVI) and intra-thoracic blood volume index (ITBVI), pulmonary vascular permeability index (PVPI) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) were compared at the time before weaning, 0.5 hour after weaning, 0.5 hour after extubation, and time of weaning failure or 48 hours after weaning. The patients in weaning failure group were sub-divided into high PVPI group (PVPI≥1.5 ml/m(2)) and low PVPI group (PVPI<1.5 ml/m(2)), the NT-proBNP and pulmonary blood volume (PBV) were compared between two groups. RESULTS: Before weaning, there was no statistical difference in NT-proBNP, volume parameters and EVLWI between two groups. EVLWI, GEDVI, ITBVI, PVPI and log NT-proBNP were gradually increased after weaning and extubation in two groups. The EVLWI, PVPI and log NT-proBNP were significantly higher at end point of observation in weaning failure group compared with those in successful weaning group (EVLWI: 12.81±2.13 ml/kg vs. 8.48±1.53 ml/kg, PVPI: 2.79±1.29 ml/m(2) vs. 2.19±0.94 ml/m(2), log NT-proBNP: 3.72±0.35 vs. 3.44±0.28, P<0.05 or P<0.01). GEDVI, ITBVI at 0.5 hour after weaning and end point of observation in weaning failure group were significantly higher than those in successful weaning group (0.5 hour after extubation: GEDVI 986.29±166.44 ml/m(2) vs. 856.47±149.15 ml/m(2), ITBVI: 1171.07±167.03 ml/m(2) vs. 1045.79±146.09 ml/m(2); end point of observation: GEDVI 957.00±67.25 ml/m(2) vs. 816.86±27.58 ml/m(2), ITBVI: 1184.29±209.68 ml/m(2) vs. 993.79±168.90 ml/m(2), P<0.05 or P<0.01). Sub-analysis showed that in weaning failure group, higher log NT-proBNP and PBV were found in patients with low PVPI compared with those with high PVPI (log NT-proBNP: 4.02±0.11 vs. 3.71±0.23, PBV: 507.19±25.72 ml vs. 347.85±47.52 ml, P<0.05 and P<0.01). CONCLUSIONS: Increased EVLW is the reason of pulmonary edema caused by weaning in septic shock patients, to which both hydrostatic and pulmonary permeability may contribute, and the latter could be more important. Monitoring preload parameters could help distinguish the mechanism of pulmonary edema after weaning, which may be useful in treatment.

[Significance of serum procalcitonin levels in the evaluation of severity and prognosis of patients with systemic inflammatory response syndrome].

OBJECTIVE: To observe the dynamic changes in serum procalcitonin (PCT), C-reactive protein (CRP), and white blood cell (WBC) count in systemic inflammatory response syndrome (SIRS) and their implication in assessment of illness severity and prognosis. METHODS: A prospective case control study was conducted. Seventy-two patients with SIRS in Guangdong General Hospital were enrolled in intensive care unit (ICU) from May, 2010 to June, 2011. Parameters including PCT, CRP, and WBC count were determined on the 1st, 3rd, and 5th day after admission. The patients were divided into septic group (n=49) and non-septic group (non-infectious SIRS group, n=23) according to the presence or absence of infectious. Dynamic changes in all parameters were compared between the two groups and correlation analysis was carried out on the basis of differential indexes and sequential organ failure assessment (SOFA). The clinical outcome within 28 days after admission to ICU was observed, and the patients were divided into death group (n=19) and survival group (n=53). Dynamic changes in all parameters between the two groups were compared. Relevant parameters were analyzed with area under receiver operator characteristic curve (ROC curve, AUC) to predict 28-day survival. Logistic regression analysis of the multiple factors was used to screen independent risk factors for predicting death. RESULTS: PCT level (µg/L) on 1st, 3rd, 5th day after admission were all significantly higher in septic group than those in non-septic group (1st day: 2.5±0.3 vs. 0.9±0.2, 3rd day: 1.9±0.3 vs. 0.6±0.2, 5th day: 0.9±0.1 vs. 0.5±0.1, all P<0.05), while there was no statistically significant difference in CRP and WBC between two groups. PCT level in septic group was gradually decreased with time, there were statistically significant differences between septic group and non-septic group at the different treatment time (all P<0.05), but there was no correlation between PCT and treatment duration in non-septic group. Positive statistical correlation was found between PCT and SOFA score (r=0.979, P<0.05). PCT (µg/L) and CRP levels (mg/L) on 1st, 3rd, 5th day were significantly higher in death group than those of survival group (PCT on 1st day: 2.0±0.8 vs. 0.8±0.3, 3rd day: 2.2±0.7 vs. 0.6±0.3, 5th day: 2.4±1.0 vs. 0.4±0.1; CRP on 1st day: 422±45 vs. 411±44, 3rd day: 418±39 vs. 403±52, 5th day: 392±38 vs. 382±46, all P<0.05), but WBC count showed no statistically significant difference between two groups. PCT level in survival group showed a significant lowering along with treatment duration, and statistical difference was seen by paired comparison between every two time-points (all P<0.05). There was no correlation between PCT level and treatment duration in death group, and it maintained a rather high level. No significant difference was seen in CRP and WBC between two groups with passage of time. AUC was 0.824 and 0.720, respectively, when patient's 28-day survival was predicted by PCT and CRP (both P<0.01). Logistic regression analysis of the multiple factors revealed that PCT>2.23 µg/L was independent risk factor predicting the prognosis [odds ratio (OR) was 1.773, 95% confidence interval (95%CI) 1.033 to 3.214, P=0.015]. CONCLUSIONS: Serum PCT evaluation may be helpful in differentiating sepsis and non-sepsis at early stage of disease, and also in predicting the severity of the illness and prognosis of SIRS. PCT may be one of the independent risk factors for 28-day survival.

[Effect of hydroxyethyl starch on intracranial pressure and plasma colloid osmotic pressure in rats with cerebral ischemia/reperfusion injury].

OBJECTIVE: To investigate the regulatory effect of hydroxyethyl starch on colloidal osmotic pressure (COP), and its effect on intracranial pressure (ICP) in rats with cerebral ischemia/reperfusion (I/R) injury. METHODS: Twenty four male Sprague Dawley (SD) rats were randomly divided into sham operation group, model group and the hydroxyethyl starch group, each n =8. Cerebral I/R model was reproduced by middle cerebral artery occlusion (MCAO), followed by reperfusion after ischemia for 2 hours. Rats in hydroxyethyl starch group received hydroxyethyl starch 130/0.4206 ml × kg(-1)× d(-1) ia tail vein at the beginning of reperfusion. ICP and COP were evaluated at 0, 2, 6, 12, 18, 24 hours after the surgery. The rats were sacrificed by decapitation. The water content of the right hemisphere was measured at 24 hours after the surgery, and the ratio of apoptosis of neurons was observed by immunohistochemical method. RESULTS: Two hours after surgery the ICP (mm Hg, 1 mm Hg=0.133 kPa) of model group and hydroxyethyl starch group was significantly increased compared with sham operation group (11.50 ± 1.43, 12.48 ± 0.75 vs. 7.95 ± 0.92, both P <0.05). With prolongation of time, the ICP gradually increased and reached the peak at 24 hours (22.76 ± 0.72, 23.32 ± 0.98 vs. 8.15 ± 1.09, both P <0.05). But there was no significant difference in ICP in the hydroxyethyl starch group compared with that of the model group at all time points. The COP (mm Hg) of hydroxyethyl starch group was significantly higher than the model group and sham operation group at each time point, and peaked at 6 hours after surgery (13.49 ± 0.50 vs. 12.04 ± 0.47, 12.00 ± 0.39, both P <0.01). There was no significant difference in COP between the model group and the sham operation group at all time points. The brain water content, neuronal apoptosis of hydroxyethyl starch group and model group was significantly higher than sham operation group [brain water content: (80.16 ± 0.44)%, (80.59 ± 0.67)% vs. (78.72 ± 0.52)%; neuronal apoptosis:(44.27 ± 7.86)%,(42.82 ± 7.82)%vs. (3.26 ± 0.00)%, P <0.05 or P <0.01], but there was no significant difference between the hydroxyethyl starch group and model group (both P >0.05). CONCLUSION: Intravenous injection of hydroxyethyl starch 130/0.4 can increase the plasma COP, but it can not significantly reduce ICP and brain water content, and it also can not improve the neuronal apoptosis.

A comparative study on the efficacy of 10% hypertonic saline and equal volume of 20% mannitol in the treatment of experimentally induced cerebral edema in adult rats.

BACKGROUND: Hypertonic saline and mannitol are commonly used in the treatment of cerebral edema and elevated intracranial pressure (ICP) at present. In this connection, 10% hypertonic saline (HS) alleviates cerebral edema more effectively than the equal volume of 20% mannitol. However, the exact underlying mechanism for this remains obscure. This study aimed to explore the possible mechanism whereby 10% hypertonic saline can ameliorate cerebral edema more effectively than mannitol. RESULTS: Adult male Sprague-Dawley (SD) rats were subjected to permanent right-sided middle cerebral artery occlusion (MCAO) and treated with a continuous intravenous infusion of 10% HS, 20% mannitol or D-[1-3H(N)]-mannitol. Brain water content (BWC) as analyzed by wet-to-dry ratios in the ischemic hemisphere of SD rats decreased more significantly after 10% HS treatment compared with 20% mannitol. Concentration of serum Na+ and plasma crystal osmotic pressure of the 10% HS group at 2, 6, 12 and 18 h following permanent MCAO increased significantly when compared with 20% mannitol treated group. Moreover, there was negative correlation between the BWC of the ipsilateral ischemic hemisphere and concentration of serum Na+, plasma crystal osmotic pressure and difference value of concentration of serum Na+ and concentration of brain Na+ in ipsilateral ischemic hemisphere in the 10% HS group at the various time points after MCAO. A remarkable finding was the progressive accumulation of mannitol in the ischemic brain tissue. CONCLUSIONS: We conclude that 10% HS is more effective in alleviating cerebral edema than the equal volume of 20% mannitol. This is because 10% HS contributes to establish a higher osmotic gradient across BBB and, furthermore, the progressive accumulation of mannitol in the ischemic brain tissue counteracts its therapeutic efficacy on cerebral edema.