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Objective:To investigate the role of cholinergic anti-inflammatory pathway in the regulation of peptide transporter 1 (PepT1) expression in small intestinal epithelium of septic rats by Ghrelin.Methods:One hundred adult male Sprague-Dawley (SD) rats were randomly divided into sham operation group, sepsis group, sepsis+vagotomy group, sepsis+Ghrelin group, and sepsis+vagotomy+Ghrelin group, with 20 rats in each group. In the sham operation group, the cecum was separated after laparotomy, without ligation and perforation. In the sepsis group, the rats received cecal ligation puncture (CLP). In the sepsis+vagotomy group, the rats received CLP and vagotomy after laparotomy. In the sepsis+Ghrelin group, 100 μmol/L Ghrelin was intravenously injected after CLP immediately. The rats in the sepsis+vagotomy+Ghrelin group received CLP and vagotomy at the same time, then the Ghrelin was intravenously injected immediately with the same dose as the sepsis+Ghrelin group. Ten rats in each group were taken to observe their survival within 7 days. The remaining 10 rats were sacrificed 20 hours after the operation to obtain venous blood and small intestinal tissue. The condition of the abdominal intestine was observed. The injury of intestinal epithelial cells was observed with transmission electron microscopy. The contents of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) in serum and small intestinal tissue were detected by enzyme-linked immunosorbent assay (ELISA). The brush border membrane vesicle (BBMV) was prepared, the levels of mRNA and protein expression of PepT1 in the small intestinal epithelium were detected by real-time fluorescence quantitative polymerase chain reaction (RT-qPCR) and Western blotting.Results:All rats in the sham operation group survived at 7 days after operation. The 7-day cumulative survival rate of rats in the sepsis group was significantly lower than that in the sham operation group (20% vs. 100%, P < 0.05). The cumulative survival rate of rats after Ghrelin intervention was improved (compared with sepsis group: 40% vs. 20%, P < 0.05), but the protective effect of Ghrelin was weakened after vagotomy (compared with sepsis+Ghrelin group: 10% vs. 40%, P < 0.05). Compared with the sham operation group, in the sepsis group, the small intestine and cecum were dull red, the intestinal tubules were swollen and filled with gas, the intestinal epithelial cells were seriously injured under transmission electron microscopy, the levels of TNF-α and IL-1β in serum and small intestinal were significantly increased, and the expression levels of PepT1 mRNA and protein in the small intestinal epithelium were significantly decreased. It indicated that the sepsis rat model was successfully prepared. After vagotomy, the intestinal swelling and gas accumulation became worse in septic rats, leading to the death of all rats. Compared with the sepsis group, the abdominal situation in the sepsis+Ghrelin group was improved, the injury of intestinal epithelial cells was alleviated, the serum and small intestinal TNF-α and IL-1β were significantly decreased [serum TNF-α (ng/L): 253.27±23.32 vs. 287.90±19.48, small intestinal TNF-α (ng/L): 95.27±11.47 vs. 153.89±18.15, serum IL-1β (ng/L): 39.16±4.47 vs. 54.26±7.27, small intestinal IL-1β (ng/L): 28.47±4.13 vs. 42.26±2.59, all P < 0.05], and the expressions of PepT1 mRNA and protein in the small intestinal epithelium were significantly increased [PepT1 mRNA (2 -ΔΔCt): 0.66±0.05 vs. 0.53±0.06, PepT1 protein (PepT1/GAPDH): 0.80±0.04 vs. 0.60±0.05, both P < 0.05]. Compared with the sepsis+Ghrelin group, after vagotomy in the sepsis+vagotomy+Ghrelin group, the effect of Ghrelin on reducing the release of inflammatory factors in sepsis rats was significantly reduced [serum TNF-α (ng/L): 276.58±19.88 vs. 253.27±23.32, small intestinal TNF-α (ng/L): 144.28±12.99 vs. 95.27±11.47, serum IL-1β (ng/L): 48.15±3.21 vs. 39.16±4.47, small intestinal IL-1β (ng/L): 38.75±4.49 vs. 28.47±4.13, all P < 0.05], the up-regulated effect on the expression of PepT1 in small intestinal epithelium was lost [PepT1 mRNA (2 -ΔΔCt): 0.58±0.03 vs. 0.66±0.05, PepT1 protein (PepT1/GAPDH): 0.70±0.02 vs. 0.80±0.04, both P < 0.05], and the injury of small intestinal epithelial cells was worse. Conclusion:Ghrelin plays a protective role in sepsis by promoting cholinergic neurons to inhibit the release of inflammatory factors, thereby promoting the transcription and translation of PepT1.
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Objective:To investigate the role of LncRNA-TUG1 in the injury of intestinal epithelial cells induced by lipopolysaccharide (LPS).Methods:LPS was used to treat HIEC-6 human intestinal epithelial cells for 24 h to construct a sepsis injury model. Whole transcriptome RNA sequencing was used to analyze the expression changes of mRNA, microRNA and lncRNA in HIEC-6 cells after LPS treatment. Real-time fluorescence quantitative (qRT-PCR) and Western blot was performed to detect the expression changes of lncRNA-TUG1, microRNA-132-3p (miR-132-3p), SIRT1 mRNA and SIRT1 protein in HIEC-6 cells after LPS treatment. The expression levels of LncRNA-TUG1, miR-132-3p and SIRT1 were artificially changed by in vitro transfection. qRT-PCR and Western blot were used to confirm the regulatory effect of lncRNA-TUG1 on microRNA-132-3p and SIRT1. CCK-8 and flow cytometry were used to analyze the effects of LncRNA-TUG1, miR-132-3p and SIRT1 on the proliferation and apoptosis of HIEC-6 cells. The dual luciferase report analysis was used to verify the targeting relationship between LncRNA-TUG1, miR-132-3p and SIRT1. Statistical analysis was performed using SPSS 17.0, and differences between the two groups were compared using independent sample t test. Results:RNA sequencing results showed that the expressions of lncRNA-TUG1 and SIRT1 were decreased in HIEC-6 cells after LPS treatment ( t=3.26, P<0.05 and t=2.55, P<0.05), but the expression of miR-132-3p was increased ( t=4.12, P<0.05). In vitro cell experiments, the expression of lncRNA-TUG1 and SIRT1 were decreased in HIEC-6 cells treated with LPS ( t=5.69, P<0.05 and t=5.712, P<0.05), while the expression of miR-132-3p was increased ( t=3.88, P<0.05). Overexpression of lncRNA-TUG1 increased the proliferation rate ( t=6.55, P<0.05) and decreased the apoptosis rate ( t=3.94, P<0.05) of LPS-treated cells. Upregulation of lncRNA-TUG1 decreased the expression of miR-132-3p ( t=4.66, P<0.05), and increased the mRNA and protein levels of SIRT1 ( t=3.91, P<0.05). Transfection of miR-132-3P mimic could inhibit the mRNA ( t=4.08, P<0.05) and protein levels of SIRT1. In LPS-treated cells, the cells co-transfected with miR-132-3pmimic and siRNA-SIRT1 had a lower proliferation rate ( t=4.55, P<0.05 and t=5.67, P<0.05) and a higher apoptosis rate ( t=3.90, P<0.05 and t=4.22, P<0.05) than those transfected with only pcDNA3.1-lncRNA-TUG. Conclusions:lncRNA-TUG1 may act as a ceRNA to regulate miR-132-3p/SIRT1, therefore alleviating HIEC-6 cell injury caused by LPS. Intervention of lncRNA-TUG1/miR-132-3p/SIRT1 regulatory pathway may become a potential strategy to prevent sepsis-induced intestinal mucosal damage.
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Objective:To investigate the related risk factors for the prognosis of hospital-acquired carbapenem-resistant Klebsiella pneumoniae (CRKP) bloodstream infections in elderly patients with critical illness.Methods:Clinical data of elderly patients with nosocomial CRKP bloodstream infection in intensive care unit (ICU) from Jan. 2010 to Dec. 2016 were retrospectively analyzed. Patients were divided into the death and survival groups according to the prognosis. Clinical characteristics were compared between the two groups. Influencing factors for the prognosis of nosocomial CRKP bloodstream infections in elderly ICU patients were screened by multivariate Logistic regression analysis.Results:A total of 119 elderly ICU patients with nosocomial CRKP bloodstream infection were enrolled. The overall ICU mortality rate was 62.2% (74/119 patients), among which the ICU mortality was lower in patients treated with tigecycline than without tigecycline treatment (50.0% or 25/50 vs. 71.0% or 49/69, χ2=4.770, P=0.029). And the ICU mortality was lower in patients with combination therapy than with mono-therapy (54.9% or 39/71 vs. 72.9% or 35/48, χ2=3.940, P=0.047). Multivariate Logistic regression analysis revealed that the administration of vasoactive drugs ( OR=25.545, 95% CI: 9.743-52.242, P=0.001), and the resistance to tigecycline ( OR=8.990, 95% CI: 0.957-24.488, P=0.049) were independent risk factors for ICU mortality. While the early initiated appropriate antibiotics treatment, which was defined as using at least one susceptible antibiotic within 48 hours ( OR=0.081, 95% CI: 0.014-0.463, P=0.005), and appropriate antibiotics and adequate duration ( OR=0.785, 95% CI: 0.631-0.977, P=0.030), were protective factors for the good outcome. Conclusions:Nosocomial CRKP bloodstream infection in elderly ICU patients leads a high ICU mortality rate. The early initiated appropriate antibiotics treatment and optimum antibiotics duration could reduce the risk for death.
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Objective:To investigate the different outcomes of two types of acute kidney injury (AKI) according to standard of Kidney Disease: Improving Global Outcomes-AKI (KDIGO-AKI), and to analyze the risk factors that affect the prognosis of intensive care unit (ICU) patients in China.Methods:A secondary analysis was performed on the database of a previous study conducted by China Critical Care Clinical Trial Group (CCCCTG), which was a multicenter prospective study involving 3 063 patients in 22 tertiary ICUs in 19 provinces and autonomous regions of China. The demographic data, scores reflecting severity of illness, laboratory findings, intervention during ICU stay were extracted. All patients were divided into pure AKI (PAKI) and acute on chronic kidney disease (AoCKD). PAKI was defined as meeting the serum creatinine (SCr) standard of KDIGO-AKI (KDIGO-AKI SCr) and the estimated glomerular filtration rate (eGFR) at baseline was ≥ 60 mL·min -1·1.73 m -2, and AoCKD was defined as meeting the KDIGO-AKI SCr standard and baseline eGFR was 15-59 mL·min -1·1.73 m -2. All-cause mortality in ICU within 28 days was the primary outcome, while the length of ICU stay and renal replacement therapy (RRT) were the secondary outcome. The differences in baseline data and outcomes between the two groups were compared. The cumulative survival rate of ICU within 28 days was analyzed by Kaplan-Meier survival curve, and the risk factors of ICU death within 28 days were screened by Cox multivariate analysis. Results:Of the 3 063 patients, 1 042 were enrolled, 345 with AKI, 697 without AKI. The AKI incidence was 33.11%, while ICU mortality within 28 days of AKI patients was 13.91% (48/345). Compared with PAKI patients ( n = 322), AoCKD patients ( n = 23) were older [years old: 74 (59, 77) vs. 58 (41, 72)] and more critical when entering ICU [acute physiology and chronic health evaluation Ⅱ (APACHEⅡ) score: 23 (19, 27) vs. 15 (11, 22)], had worse basic renal function [eGFR (mL·min -1·1.73 m -2): 49 (38, 54) vs. 115 (94, 136)], more basic complications [Charlson comorbidity index (CCI): 3 (2, 4) vs. 0 (0, 1)] and higher SCr during ICU stay [peak SCr for diagnosis of AKI (μmol/L): 412 (280, 515) vs. 176 (124, 340), all P < 0.01]. The mortality and RRT incidence within 28 days in ICU of AoCKD patients were significantly higher than those of PAKI patients [39.13% (9/23) vs. 12.11% (39/322), 26.09% (6/23) vs. 4.04% (13/322), both P < 0.01], while no significant difference was found in the length of ICU stay. Kaplan-Meier survival curve analysis showed that the 28-day cumulative survival rate in ICU in AoCKD patients was significantly lower than PAKI patients (Log-Rank: χ2 = 5.939, P = 0.015). Multivariate Cox regression analysis showed that admission to ICU due to respiratory failure [hazard ratio ( HR) = 4.458, 95% confidence interval (95% CI) was 1.141-17.413, P = 0.032], vasoactive agents treatment in ICU ( HR = 5.181, 95% CI was 2.033-13.199, P = 0.001), and AoCKD ( HR = 5.377, 95% CI was 1.303-22.186, P = 0.020) were independent risk factors for ICU death within 28 days. Conclusion:Further detailed classification (PAKI, AoCKD) based on KDIGO-AKI SCr standard combined with eGFR is related to ICU mortality in critical patients within 28 days.
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objective:To investigate the tolerability of early enteral nutrition (EN), and to further explore the association of early EN with clinical outcome in critically ill patients with hemodynamic instability.Methods:The adult patients from Zhejiang Provincial People’s Hospital with an expected admission to ICU for at least 24 h were consecutively recruited from May 2014 to May 2016, and all clinical, laboratory, and survival data were prospectively collected. The AGI grade was daily assessed on the first week of ICU admission. Enteral nutrition (EN) started after 6 h of hemodynamic stability (MAP ≥ 65 mmHg) when the patients took vasoactive medication. The patients were divided into three groups based on the timing of EN initiation: early EN group (EN initiation within 48 h of ICU admission), late EN group (EN initiation at more than 48 h of ICU admission), and no initiation of enteral feeding within 7 days of ICU admission.Results:Of 201 patients enrolled, the mean age was 65.3 ± 16.4 years, APACHE II score was 22.4 ± 6.85, and 191 patients (95.0%) took mechanical ventilation. There were no differences in high gastric residual volume, diarrhea, and gastrointestinal (GI) bleeding between the early EN group and late EN group ( P>0.05). Whereas, patients in the no initiation of EN within 7 days of ICU admission had a lower prevalence of gastric residual volume (16.7% vs. 33.3%, P=0.05), but higher prevalence of GI bleeding (47.2% vs. 26.1%, P=0.02). Compared with those in the late EN group and in no initiation of EN within 7 days of ICU admission, patients in the early EN group had lower 28- (30.4% vs. 47.9% vs. 55.6%, P=0.01) and 60-day mortality rates (38.0% vs. 53.4% vs. 63.9%, P=0.017). Multivariate Cox regression analysis showed that the timing of EN initiation on the admission to ICU (early EN vs. late EN, χ 2≥5.83, P<0.05; early EN vs. no initiation of EN, χ 2≥7.90, P<0.01), serum creatinine ( χ 2=5.06, P<0.05), plasma albumin ( χ 2≥6.41, P<0.01), AGI grade ( χ 2≥8.15, P<0.01), and APACHE II score ( χ 2≥9.62, P<0.01) were independent predictors for 28- and 60-day mortality. Conclusions:Early EN on admission to ICU could be tolerated, and is significantly associated with lower risk of 28- and 60-day mortality in critically ill patients with vasoactive medication to maintain hemodynamic stability.
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Objective To investigate the prevalence of feeding intolerance (FI),and to explore the FI within 7 days of ICU admission in association with clinical outcome in critically ill patients.Methods The adult patients from 14 general ICUs in Zhejiang Province with an expected admission to ICU for at least 24h were recruited from March 2014 to August 2014,and all clinical,laboratory,and survival data were prospectively collected.The AGI (acute gastrointestinal injury) grade was daily assessed based on gastrointestinal (GI) symptoms,feeding details and organ dysfunction within the first week of ICU stay.The intra-abdominal pressures (IAP) was measured using AbViser device.Results Of 550 patients enrolled,418 were assessed in GI symptoms and feeding details within 7 days of ICU stay.The mean age and SOFA score were (65.1 ± 18.3) years and (8.96 ±4.10),respectively.Of them,355 patients (84.9％) were under mechanical ventilation support,and 37 (8.85％) received renal replacement therapy.The mean length of time for enteral feeding was (30.8 ±26.2) h,and the prevalence of FI on the 3rd and 7th day of ICU stay accounted for 39.2％ and 25.4％,respectively.Compared to those with FI within 7 days of ICU stay,the patients without FI had higher rate of successively weaning from mechanical ventilation (21.3％ vs.5.7％,P =0.003) and higher rate of withdrawal of vasoactive medication (45.5％ vs.20.0％,P =0.037),as well as lower mortality rate of 28-day (24.4％ vs.38.7％,P =0.004) and 60-day (29.6％ vs.44.3％,P =0.005).In multivariate Cox regression model with adjustment for age,sex,participant center,serum creatinine and lactate,AGI grade on the first day of ICU stay,and comorbidities,the FI within 7 days of ICU stay (x2 ≥ 7.24,P ＜ 0.01) remained to be independent predictors for 60-day mortality.After further adjusted for SOFA score,the FI within 7 days of ICU stay (HR =1.71,95％ CI:1.18-2.49;P =0.006) and AGI grade on the first day of ICU stay (HR =1.33,95 ％ CI:1.07-1.65;P =0.009) could provide independent prognostic values of 60-day mortality.Conclusions There is high rate of FI occurred within 7 days of ICU stay,and is significantly associated with worse outcome.In addition,this study also provides evidence to further support that measurement of gastrointestinal dysfunction could increase value of SOFA score in outcome prediction for the risk of 60-day mortality.
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Objective:To evaluate the clinical application value of gastrointestinal contrast-enhanced ultrasound combined gas injection method in verifying the location of nasointestinal tube in critically ill patients.Methods:Data of 60 critically ill patients who had the indications of indwelling nasointestinal tube were collected from September 1,2015 to September 1,2016 in the Intensive Care Unit of Zhejiang Provincial People(s) Hospital.The position of nasointestinal tube in patients who underwent bedside blind insertion would be confirmed routinely through gas injection auscultation method.After tube was inserted,its route was scanned by ultrasound with gas perfusion assistance.Afterwards,rapid gas perfusion was used until suspicious tube end position was determined.Furthermore,oral ultrasound contrast agent was injected into the tube if instantaneous strong echo of gas was observed in localized lumen,and contrast agent filling meant the placement being successful.Two methods of position confirmation of nasointestinal tube in critically ill patients included gastrointestinal contrast enhanced ultrasound combined gas injection and gas injection auscultation only,and the effect of the two methods was compared and confirmed by chest and abdominal X ray examinations to verify the location of nasointestinal tube below pylorus.Results:A total of 60 patients were included in this study,58 patients(96.7％)in gastrointestinal contrast enhanced ultrasound combined gas injection group were successfully positioned.Among them,the placements of tube in 56 cases were below pylorus,while 2 cases were above pylorus.The sensitivity,specificity,positive predictive value,negative predictive value and accuracy of location of gastrointestinal contrast enhanced ultrasound combined gas injection method were 96.6％,100％,100％,50％,96.7％ and of gas injection auscultation method were 74.1％,50％,97.7％,6.3％ and 73.3％.The differences of the sensitivity,specificity,negative predictive value and accuracy between the two methods were statistically significant (P ＜ 0.05).Conclusion:Gastrointestinal contrastenhanced ultrasound combined gas injection method is a safe,simple and convenient method with high sen-sitivity,specificity,negative predictive value and accuracy in confirming the location of the nasointestinal tube.
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Objective To investigate the risk factors of thrombopenia(TP)in septic patients complicated with acute kidney injury (AKI).Methods Two hundred and sixty five septic patients complicated with AKI admitted in Intensive Care Unit ICU of Zhejiang Provincial People''s Hospital during January 2012 and December 2016 were enrolled in the study.The clinical data, results of laboratory tests, Acute Physiology and Chronic Health Evaluation (APACHEII) scores, Sequential Organ Failure Assessment (SOFA) scores, therapeutic intervention, and 28-day mortality were documented.Among 265 patients, TP occurred within 7 days in 112 cases (TP group) and did not occur in 153 cases (non-TP group).Multivariable Logistic regression analysis was performed to analyze the risk factors of TP.Results The 28-day mortality rate in TP group was higher in TP group than that in non-TP group (47.3% vs.33.3%, χ2=5.307,P<0.05).Univariate analysis showed that age, C-reactive protein (CRP), procalcitonin (PCT) and APACHEII score, SOFA score, continuous renal replacement therapy (CRRT), heparin anticoagulation, shock, usage of linezolid and bloodstream infections were associated with TP in septic patients with AKI(all P<0.05).Multivariable Logistic regression analysis showed that age≥65 (OR=4.53, 95%CI 1.23-9.24,P<0.05), CRRT(OR=5.24,95%CI 2.14-14.56,P<0.01), heparin anticoagulation(OR=4.56,95%CI 2.13-8.46,P<0.01), usage of linezolid(OR=2.35,95%CI 1.25-5.24,P<0.01), shock(OR=2.15,95%CI 1.03-4.96,P<0.01)and bloodstream infections(OR=4.26,95%CI 1.36-12.48,P<0.01)were independent risk factors for septic patients with TP.Conclusion For septic patients with AKI having these risk factors, the platelet counts should be closely monitored, and intervention measures should be given to reduce the occurrence of TP.
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Objective To investigate the effects and mechanism of microRNA150 (miRNA150) on proliferation, invasion and metastasis of gastric cancer.Methods From January 2015 to June 2016, 45 surgical specimens were collected.The expression of miRNA150 and Ras-interacting protein 1(RASIP1) at miRNA level in gastric cancer tissues and paracancerous tissues were quantified by quantitative real-time fluorescent reverse transcriptase-polymerase chain reaction (qRT-PCR).The correlation between miRNA150 and the biological features of gastric cancer as well as RASIP1 expression was analyzed.Gastric cancer cell line SGC-7901 was cultured and transfected with pcDNA3.1-miRNA150 expression plasmids.The effect of miRNA150 over-expression on the proliferation of SGC-7901 cells was determined by 3-(4,5-dimethyl-2-thiazolyl)-2,5-dipheayl 2-H-tetrazolium bromide (MTT) assay.And the effect of miRNA150 over-expression on the invasion and metastasis of SGC-7901 cells was detected by Transwell assay.The potential target gene of miRNA150 was analyzed by bioinformatics software and dual-luciferase reporter assay system.The effect of miRNA150 over-expression on RASIP1 expression in SGC-7901 cells was tested by qRT-PCR and Western blotting.Analysis of variance and t test were used to compare normal distribution data.And the Mann-Whitney rank sum test was used to compare skewed distribution data.Spearman assay was used for correlation analysis.Results The median level of miRNA150 in gastric cancer tissue was higher than that of paracancerous tissues (3.85, 0.26 to 7.92 vs 1.98, 0.19 to 5.66), and the difference was statistically significant (U=466.22,P<0.05).The median level of RASIP1 mRNA in gastric cancer tissue (1.65, 0.13 to 3.59) was lower than that of paracancerous tissues (2.96, 0.59 to 6.08), and the difference was statistically significant (U=522.31,P<0.05).The results of correlation analysis indicated that RASIP1 expression level was negatively correlated with miRNA150 expression (r=-0.589, P=0.008).The RASIP1 expression at mRNA level was negatively correlated with miRNA150 expression (r=-0.614, P=0.004).The dual-luciferase reporter assay showed RASIP1 was the target gene of miRNA150.The miRNA150 expression level was related with tumor size, TNM staging and lymph node metastasis(χ2=5.81, 6.00 and 10.04,all P<0.05).The results of MTT assay showed that after SGC-7901 cells cultured for 24 hours, the A value of pcDNA3.1-miRNA150 plasmid transfected cells was higher than that of the untransfected SGC-7901 cells (0.51±0.04 vs 0.79±0.03), and the difference was statistically significant (t=4.745, P<0.05).The results of Transwell assay indicated that there were more invasive and metastatic cells in pcDNA3.1-miRNA150 plasmid transfected cells.The results of qRT-PCR showed that the relative levels of RASIP1 mRNA in control group, pcDNA3.1-miRNA150 plasmid transfected cells and pcDNA3.1 empty plasmid transfected cells were 1.00±0.02, 0.51±0.03 and 1.08±0.03, respectively.The RASIP1 mRNA level in pcDNA3.1-miRNA150 plasmid transfected cells was lower than untransfected and pcDNA3.1 empty plasmid transfected cells, and the differences were statistically significant (t=3.940, 4.120, both P<0.05).miRNA150 could negtively regulate the RASIP1 protein expression and promote the proliferation and invasion of gastric cacer cells.Conclusions Over-expression of miRNA150 induced invasion and metastasis of gastric cancer by down-regulating RASIP1 expression.miRNA150 may be a novel biomarker for the diagnosis and treatment of tumor metastasis.
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Objective To discuss the effects of pressure control (PC) and positive end-expiratory pressure (PEEP) incremental method lung recruitment maneuver (RM) on haemodynamics in piglets with acute lung injury (ALI) induced by paraquat (PQ) poisoning. Methods The ALI/acute respiratory distress syndrome (ARDS) model was reproduced by intraperitoneal injection of 20% PQ (20 mL) in 10 healthy female piglets, and they were randomly divided into PC lung RM group (RM1 group) and PEEP incremental method lung RM group (RM2 group), with 5 piglets in each group. Heart rate (HR), mean arterial pressure (MAP), and cardiac index (CI) were monitored by pulse-indicated continuous cardiac output (PiCCO) monitoring before model reproduction (baseline), on the time of successfully set up of model and at 5, 15 and 30 minutes after RM. At the same time the arterial partial pressure of oxygen (PaO2) and arterial partial pressure of carbon dioxide (PaCO2) were recorded, and oxygenation index was calculated. Lung tissues were collected before model reproduction, on the time of successfully set up of model, and at 30 minutes after RM respectively, and pulmonary pathology changes were observed after hematoxylin and eosin (HE) staining under light microscopy. Results The HR, MAP, and PaCO2 on the time of successfully set up of model in both groups were increased obviously while CI, PaO2, and oxygenation index were decreased obviously as compared with those at baseline, all of which conformed to the expression of ALI/ARDS. With RM time extended, the HR in both groups was declined while MAP and CI were increased gradually. The HR and MAP at 5 minutes after RM of RM1 group were significantly lower than those of the RM2 group [HR (bpm): 126.8±5.2 vs. 134.0±3.8, MAP (mmHg, 1 mmHg = 0.133 kPa): 98.4±3.3 vs. 102.8±2.6, both P 0.05). The lung tissue in both groups showed a variety of pathological changes at 30 minutes after RM. The main performances were the loss of alveolar epithelial cells, the further wideness of alveolar interval and the distension of alveolar, and the part breakage of alveolar interval. The wideness of alveolar interval was more significant in RM2 group than that of RM1 group, and alveolar cleft was more common too. Conclusion Both PC and PEEP incremental method lung RM can improve the oxygenation of the piglets with ALI/ARDS induced by PQ, and the PC lung RM has less impact on haemodynamics.
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Objective To investigate the value of clinical data used for conventional indications of initiating renal replacement therapy (RRT) such as serum creatinine (SCr),blood urea nitrogen (BUN) and acute renal injury (AKI) stage and in estimating the prognosis of critically ill patients with AKI.Methods A retrospective analysis of 258 AKI adult inpatients treated with continuous renal replacement therapy (CRRT) in ICU from Jan.2011 to Jan.2015.According to the outcomes,all subjects were divided into survival group (n =104)and death group (n =154).The general condition,AKI causes,results of renal function (urine output,SCr,BUN and AKI stage),homeostasis (acid-base balance and electrolyte level),severity of disease (APACHE Ⅱ score and SOFA score) and others were compared between two groups.Additionally,risk factors for the prognosis of critically ill patients with AKI were screened by the multivariate Cox's proportional hazard models and the receiver operating characteristic (ROC) curve.Results There were no significant differences in gender,age,primary disease,AKI causes,APACHE Ⅱ score,renal function (urine output,SCr,BUN and AKI stage),serum potassium level and phosphorus level between two groups before CRRT (P ＞ 0.05),but more patients in death group had severe sepsis (31.17％ vs.19.23％,P =0.033),lower pH value [(7.27 ±0.34)vs.(7.41 ±0.34),P =0.024] and higher level of lactate [(3.97 ±2.87) vs.s (2.64 ± 2.30),P =0.006].After the analysis with multivariate Coxg proportional hazard models,it was found that the levels of serum phosphorus (P =0.043) and lactate (P =0.009) were the independent risk factors for prognosis of critically ill patients with AKI,and other conventional indications for initiating RRT such as SCr,BUN,AKI stage,urine output,pH,bicarbonate level or potassium level were not closely associated with the prognosis of patients (P ＞ 0.05).Therefore,a composite of these six variables (pH,bicarbonate level,phosphorus level,potassium level,urine output and AKI stage) was analyzed.According to the analysis result of ROC curve,the diagnostic value of combined six different variables in predicting in-hospital mortality of AKI patients [area under the curve (AUC) 0.669,95％ CI:0.577-0.762] was almost as high as that of lactate (AUC:0.683,95％ CI:0.590-0.777),and significantly higher than SCr (AUC:0.460,95％ CI:0.358-0.562),BUN (AUC:0.469,95％ CI:0.366-0.571).Conclusions This composite of six different variables is more useful than any other conventional indications for initiating RRT in predicting post-AKI mortality.As a result,a composition of six different variables should be considered rather than any single variable alone for indication of initiating RRT in critically ill patients with AKI.
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ObjectiveTo investigate the incidence of hypomagnesemia and the effect of serum magnesium levels on the prognosis of critically ill patients in intensive care unit (ICU).Methods A single-center prospective observation was conducted. The adult patients admitted to ICU of Zhejiang Provincial People's Hospital from January 2012 to January 2014 were enrolled, and they were expected to stay in hospital for more than 48 hours. All the patients who had been diagnosed with hypomagnesemia before ICU admission, or those who had received magnesium supplement therapy were excluded. All patients were monitored for serum magnesium levels within 24 hours after ICU admission, and they were divided into three groups: normomagnesemic group (serum magnesium levels 0.7-1.2 mmol/L), hypomagnesemic group (serum magnesium levels 1.2 mmol/L). Various parameters were recorded for every patient, including general information, disease composition, laboratory indexes, duration of mechanical ventilation, ICU stay days and final outcome. The acute physiology and chronic health evaluationⅡ (APACHEⅡ) score and sequential organ failure assessment (SOFA) score during the first 24 hours after ICU admission were calculated. The risk factors for the death in critically ill patients were postulated by logistic regression analysis.Results A total of 374 critically ill patients were enrolled, with 242 patients (64.71%) in normomagnesemic group, 102 (27.27%) in hypomagnesemic group, and 30 (8.02%) in hypermagnesemic group. As to the disease composition, although the patients in normomagnesemic group and hypomagnesemic group were mainly consisted of patients with nervous system diseases (33.06%, 31.37%) or pneumonia(25.62%, 25.49%), the proportion of patients with major abdominal and thoracic surgery (15.69% vs. 5.78%,χ2= 8.837, P= 0.003) or severe sepsis (7.84% vs. 1.65%,χ2= 9.935,P= 0.007) was significantly greater in the hypomagnesemic group compared with that of normomagnesemic group, and most hypermagnesemic patients were complicated by renal dysfunction in different degrees. Compared with the normomagnesemic group, the hypomagnesemic group was found to have higher SOFA scores (6.86±3.12 vs. 5.46±2.75,t= -2.930,P= 0.004), longer stay in ICU (days: 15.98±13.29 vs. 12.43±7.14,t= -2.318,P= 0.034) and higher mortality [54.90% (56/102) vs. 33.88% (82/242),χ2= 6.587, P= 0.010], but no statistically significant differences were found in gender composition, age, levels of other electrolytes (natrium, potassium, calcium, phosphorus), and APACHEⅡ score. As shown by the result of the logistic regression analysis, APACHEⅡ score [odds ratio (OR) = 1.129, 95% confidence interval (95%CI) = 1.064-1.197,P= 0.000] and serum magnesium level (OR= 2.163, 95%CI= 1.015-4.610,P= 0.046) were independent risk factors for death in critically ill patients.Conclusion Serum magnesium levels are closely related to mortality rate in patients in ICU, so more attention should be paid to the occurrence of hypomagnesemia in critically ill patients.
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Objective To investigate the association between genetic polymorphisms of Dectin-2 and pulmonary cryptococcosis.Methods A total of 134 non-human immunodeficiency virus (HIV)patients with pulmonary cryptococcosis and 464 healthy controls were included in this case control study.The peripheral leucocyte DNA was extracted and genotyping was performed by multiplex SNaPshot technology.The single nucleotide polymorphism (SNP)of rs11045418 located at 5′-flanking locus of Dectin-2 gene was genotyped.Patients without predisposing conditions were compared independently.The differences of gene polymorphism distributions compared between pulmonary patients and healthy control, and between patients without predisposing conditions and healthy control.All data were analyzed withχ2 tests.Results Among the total 134 patients,82 patients had no predisposing factors.Thirty two patients met the proven diagnosis criteria and 102 patients were probable pulmonary cryptococcosis.According to the site of infection, 72 patients had local infection in lungs and 62 patients had disseminated cryptococcosis.Three samples failed in genotyping,one of which was a patient without predisposing factor.Compared with the control group,there was a trend of increasing proportion of heterozygote rs11045418 CT in the 131 pulmonary cryptococcosis patients (59% vs 50%,P =0.069,OR=1.44,95%CI :0.97-2.13),and the heterozygote was significantly increased in 81 patients without predisposing conditions(64% vs 50%,P =0.017,OR= 1 .82,95 %CI :1 .11 -2.95 ).No significant difference of genotype distribution was found between the local and disseminated infection patients.Conclusion Our study shows that rs11045418 CT heterozygote in Dectin-2 is associated with the susceptibility of pulmonary cyrptococcosis among non-HIV-infected Chinese patients,which indicated that the change of Dectin-2 receptor may play a role in the pathogenesis of pulmonary cyrptococcosis.
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Objective To evaluate the early diagnostic values of soluble triggering receptor expressed on myeloid cell-1 (sTREM-1) in patients with ventilator associated pneumonia (VAP).Methods A total of 112 clinical suspicion VAP ventilator-associated pneumonia (VAP) patients accepted from January 2008 through December 2010 were enrolled for prospective and observational study.Two independent intensivists without aware of the results of the sTREM-1 assay separately made diagnosis of VAP present or absent depending on the clinical symptoms and results of microbial culture.Patients were categorized into two groups:VAP group (n =74) and non-VAP group (n =38).The levels of sTREM-1 in broncho-alveolar lavage fluid (BALF) collected with Gibot method in unemployment of bronchoscope and in serum were measured by enzyme-linked immunosorbent assay (ELISA) on the first day of suspected diagnosis.Comparison of sTREM-1 level between BALF and serum was made by t-test and Receiver Operating Characteristic (ROC) curve.Results A total of 112 clinical suspicion VAP patients admitted from January 2008 through December 2010 were enrolled for prospective and observational study.Two independent intensivists without aware of the results of the sTREM-1 assay made diagnosis of VAP present or absent depending on the clinical symptoms and results of microbial culture.Patients were categorized into two groups:VAP group (n =74) and non-VAP group (n =38).The levels of sTREM-1 in broncho-alveolar lavage fluid (BALF) collected with Gibot method in unemployment of bronchoscope and in serum were measured by enzyme-linked immunosorbent assay (ELISA) on the first day of suspected diagnosis.Comparison of sTREM-1 level between BALF and serum was made by t-test and Receiver Operating Characteristic (ROC) curve.Conlclusions In suspected VAP patients,measurement of sTREM-1 levels in BALF and in serum could help identify VAP in early stage.
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Objective To evaluate the prognostic factors of elderly patients with noscomial Candidemia in intensive care unit. Methods A retrospective study was carried out in 75 elderly patients with noscomial Candidemia from 2001 to 2008. Multivariate logistic regression analysis was performed to find the correlations of prognosis with clinical and biochemical parameters. Results A total of 75 Candida strains were isolated from blood. The proportion of non-albicans species reached to 70.7%. Fluconazole-resistant candidiasis was increased. Overall mortality rate was 48.0%.Multivariate logistic regression analysis showed that septic shock, comorbid bacteremia, higher serum creatinine and sequential organ failure assessment (SOFA) score more than 10 were independent predictors for in-hospital mortality (Ward=6.34, 5.15, 8.04, 6.82, all P＞0.05). Conclusions Noscomical Candidemia in elderly critical illness patients leads a high mortality, the proportion of nonalbicans species and fluconazole-resistant candidiasis increase. The blood culture and drug sensitive test should be performed routinely to provide proper evidence for antifungal therapy. Monitoring the high risk factors, effective and reasonable therapeutics are the guarantee for reducing the mortality induced by Candidemia.
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Objective To investigate the changes of CD4+CD25+ regulatory T (Treg) cells in elderly patients with septic shock, and to evaluate the effects of the changes on 28-day mortality rate.Methods The 75 consecutive elderly patients with septic shock were recruited from December 2006to December 2008, and the general states and clinical characteristics of them were analyzed. The CD4+ CD25+ FoxP3 regulatory T cells and human leucocyte antigen DR (HLA-DR) were measured by flow cytometer at the 1st, 4th and 7-10th day of septic shock after being diagnosed. Results The patients were at an average age of (69.2±7.5) years, and the 28-day mortality rate was 53.3%.There were no significant differences in the percentage of CD4 + CD25+ FoxP3/CD4+T cells between the survivors and the non-survivors at the 1st day (1.76 % ±0.31% vs. 1.68 %±0.24 %, P＞0.05)and the 4th day (1.94%±0.32% vs. 1.82% ±0.28%, P＞0.05). However, compared with the survivors, non-survivors had a higher percentage of CD4+ CD25+ FoxP3/CD4+ T cells (2.65%±0.28% vs. 1.79%±0.27%, P＜0.01) at the 7-10th day of septic shock after being diagnosed.Furthermore, from the 4th day to the 7-10th day, the expressions of monocyte HLA-DR in the nonsurvivors were significantly lower than in the survivors (P＜0. 01), and they were inversely correlated with the percentage of CD4+ CD25+ FoxP3/CD4+ T cells at the 4th day (r=-0.39, P=0.023) and the 7-10th day (r= -0. 58, P＜0. 01) respectively. The multiple logistic regression analysis showed that the percentages of CD4+ CD25+ FoxP3/CD4+ T cells (OR = 3.47, 95% CI: 1.33-10.0) and HLA-DR (OR= 0. 27, 95% CI: 0.14-0.73) were independent predictors of 28-day mortality rate.Conclusions Persistent higher percentage of CD4+ CD25+ Treg cells in the elderly patients with septic shock indicates that the patients are under the states of immunosuppression and have a higher risk ofmortality in intensive care unit at admission.
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Objective To evaluate the changes of peripheral blood CD4+CD25+ regulatory T cells and its prognostic value in sepsis patients.MethodThe percentage of CD4+CD25+/CD4+ T cells were measured by flow eytometry present in peripheral blood in 36 sepsis patients on day 1,3 and 5 and 15 healthy people (control group).The changes of CD4+CD25+ regulatory T cells were analyzed in survivors group and non-survivors group respectively.Results There were 19 survivors and 17 non-survivors in sepsis patients.The percentage of CD4+CD25+/CD4+ T cells in survivors group and non-survivors group on day 1 was significantly lower than that in eontrol group [(12.42± 3.26)%,(12.96± 3.00)% vs (16.97 ± 3.66)%,P＜0.05].The percentage of CD4+CD25+/CD4+ T cells in survivors group and non-survivors group on day 3 were both signifieanfly higher than that on day 1 [(24.47±4.62)%vs (12.42±3.26)%,(26.61±3.85)%vs (12.96±3.00)%,P＜0.05].The percentage of CD4+CD25+/CD4+ T cells in survivors group on day 5[(18.28±4.28)%]was significantly lower than that on day 3 (P＜0.05),and the percentage of CD4+CD25+/CD4+ T cells in nonsurvivors group on day 5 were significantly higher than that on day 3(P＜0.05).There was no significant difference in the percentage of CD4+CD25+/CD4+ T ceils between survivors group and non-survivors group on day 1,3 respeefively(P ＞ 0.05),but the percentage of CD4+CD25+/CD4+ T cells in survivors group was significantly lower than that in non-survivors group on day 5 (P＜0.05).Conclusions The CD4+CD25+ regulatory T cells in sepsis patients decreases following by increase after onset.The persistent increase suggests the emergence of immunoparalysis,which is followed by high monaliy,The CD4+CD25+ regulatory T cells are valuable in evaluation of immune state and prediction the prognosis in sepsis patients.
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OBJECTIVE To investigate pathogens,drug resistance and the risk factors of ventilator-associated pneumonia(VAP) in our intensive care unit(ICU).METHODS Spetum samples collected from the low respiratory trachea of the VAP patients from July 2008 to May 2009 in ICU received bacterial culture and antibiotics sensitive test.The risk factors related to VAP were identified and evaluated with Chi-square test.RESULTS 82 strains of pathogens had been isolated by culture and most of which were Gram negative bacilli(69.51%).The other pathogens included Gram positive cocci(25.61%) and fungi(4.88%).The most common pathogens were Acinetobacter calcoaceticus-baumannii,Staphylococcus aureus and Pseudomonas aeruginosa.Most of the Gram negative bacilli were highly resistant to many kind of antibiotics,especially Acinetobacter calcoaceticus-baumannii.77.8% of S.aureus were Meticillin-resistant S.aureus(MRSA),and all sensitive to Vancomycin.The duration of mechanical ventilation≥5 days,age≥65 years,gastric acid secretion inhibitor(GASI) therapy and albumen
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0.05) and was significantly lower than that in groups of GNB and mycetes' (P
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Objective To evaluate the efficacy and safety of Caspofunjin on invasive fungal infections in patients refractory to Fluconazole in ICU.Methods The open clinical trial was conducted in 44 invasive fungal infections patients who was refractory to Fluconazole,including 7 cases of confirmed,28 cases of suspected and 9 cases for empire treatment.They were treated with Caspofunjin in a dose of 70 mg in the first day,and then in a dose of 50 mg/d for 10～40 d.Results The cure rate of patients was 42.86%,the effective rate was 76.19%,and the eradication rate was 65.22%.All patients were well tolerated.Conclusion Caspofunjin is effective and safe in the treatment of severe invasive fungal infections.