RESUMO
Objective:To investigate the diagnostic and early-warning value of laboratory test indicators for sepsis-induced myocardial injury (SIMD).Methods:The clinical data of 183 patients with sepsis admitted to the Department of Emergency and Critical Care Medicine of Guangdong Provincial People's Hospital from August 2016 to October 2020 were collected. The patient's age, gender, past medical history, vital signs and pathogen culture results were extracted. Cardiac function, blood routine, liver function, renal function, inflammatory factors, coagulation function, APACHE Ⅱ and SOFA scores were recorded at enrollment and 72 h after admission. SIMD was defined as cTnT ≥300 pg/mL and NT-proBNP ≥1243 pg/mL twice in 72 h intervals between enrolled cases, and the early-warning factors of patients with SIMD were analyzed. The differences in various indicators between the two groups were compared, and Logistic regression analysis was used to explore the diagnostic efficacy of cTnT and NT-proBNP combined for SIMD, and the correlation between PCT/PLT ratio and the occurrence of SIMD.Results:Among 250 patients, 67 patients were excluded for lack of the main indicators, and 183 patients (including 62 patients with history of cardiac disease) were enrolled finally. Among 183 patients with sepsis, 105 patients (57.38%) with cTNT ≥300 pg/mL and NT-proBNP ≥1 243 pg/mL, were diagnosed as myocardial injury; after excluding 62 patients with history of cardiac disease, 59 patients (48.76%) with cTNT ≥300 pg/mL and NT-proBNP ≥1 243 pg/mL were diagnosed as myocardial injury. Logistic regression analysis showed that increased PCT/PLT ratio ( OR=1.585, 95% CI: 1.124-2.237, P=0.009) was an independent risk factor for early-warning of SIMD. The PCT/PLT ratio ( OR= 1.850, 95% CI: 1.103-3.102, P=0.020) could stably predict the occurrence of SIMD in patients without previous history of heart disease. ROC curve analysis showed that PCT/PLT ratio could effectively predict the occurrence of SIMD (AUC=0.693, 95% CI: 0.617-0.769, P<0.001), the optimal cut-off value was 0.177 (sensitivity: 65.7%, specificity: 66.7%). The PCT/PLT ratio was still effective in predicting the occurrence of SIMD after excluding patients with previous history of heart disease (AUC=0.733, 95% CI: 0.643-0.823, P<0.001), and the optimal cut-off value was 0.429 (sensitivity: 55.9%, specificity: 83.9%). Conclusions:The combination of cTnT and NT-proBNP has certain diagnostic value for SIMD, and the PCT/PLT ratio could warn the occurrence of SIMD.
RESUMO
Objective:To evaluate the predictive effect of sepsis-induced coagulopathy (SIC) score level on the prognosis of septic patients under sepsis 3.0 criteria.Methods:A retrospective single-center observational study was conducted on the septic patients admitted to the department of critical care medicine and the department of emergency in Guangdong Provincial People's Hospital from August 2016 to July 2021. The baseline data, laboratory indexes and SIC scores of the patients were collected on the first and fourth (4th) day after hospitalization. Whether the patients were survival within 30 days after enrollment was recorded. Univariate and multivariate Logistic regression were used to analyze the independent risk factors for 30-day mortality in septic patients. The receiver operator characteristic curve (ROC curve) was drawn to evaluate the predictive value of SIC score on the 30-day prognosis of septic patients.Results:A total of 173 patients met the inclusion criteria including 111 (64%) survivors and 62 (36%) non-survivors. There were significant differences in lymphocyte count (LYM), sequential organ failure assessment (SOFA), oxygenation index (PaO 2/FiO 2) and cardiovascular SOFA score between the survival group and the non-survival group. And there were no significant differences in other indexes. On the first day of admission, there were statistically significant differences in PaO 2/FiO 2, cardiovascular SOFA score, LYM, SIC score between the non-survival group and the survival group. There were significant differences in international normalized ratio (INR), prothrombin activity (PTA), prothrombin time (PT), PaO 2/FiO 2, cardiovascular SOFA score, LYM, C-reactive protein (CRP) and procalcitonin (PCT) between the two groups on the 4th day after admission. The mortality of septic patients increased with the increase of SIC score. Binary Logistic regression analysis showed that SIC score and LYM on the 4th day after admission were independent risk factors for 30-day mortality in septic patients (both P < 0.05). The ROC curve showed that SIC score had a certain predictive value for the 30-day prognosis of septic patients [area under the ROC curve (AUC) = 0.712, 95% confidence interval (95% CI) was 0.629-0.794, P < 0.001]. The predictive value of SIC score combined with LYM was better than that of the two alone (AUC = 0.748, 95% CI was 0.688-0.828, P < 0.001). Conclusions:The SIC score has a certain predictive value for the 30-day prognosis of septic patients. The predictive value of SIC score combined with LYM is better than that of the two alone, which is expected to be a potential indicator for early assessment of the condition and prognosis of septic patients.
RESUMO
Objective:To investigate the protective effect of external diaphragm pacing on the prevention of ventilator-induced diaphragm dysfunction (VIDD) in rabbits and its mechanism.Methods:Eighty-five New Zealand white rabbits were randomly (random number) divided into the blank control group (BC, n=5), spontaneous breathing group (SB, n=20), volume control ventilation group (VC, n=20), external diaphragm pacing group (EDP, n=20), external diaphragm pacing and volume control ventilation group (EDP+ VC, n=20). After successful modeling, the rabbits in each group were treated accordingly except for the BC group. Rabbitss in the BC group were not mechanically ventilated, and the diaphragm was removed immediately after anesthetizing. Whole diaphragms of 5 rabbits per time point per other group were also collected after anesthesia at post treatment hour (PTH) 6 and on post treatment day (PTD) 1, 3, and 7. Diaphragm weight/body weight and diaphragm isometric contractile force of each group were measured. The pathological changes of diaphragmatic tissues were observed by HE staining. The protein expressions of Cyt c, RyR1, caspase-3, and p-mTORC1 were measured by Western blot. Repeated measures analysis of variance was used for the comparison between multiple groups of variables at different time points, and LSD- t test was used for the further comparison between two groups at the same time point, a P<0.05 was considered statistically significant. Results:Compared with the BC group, the VC group showed diaphragmatic pathological changes conformed to VIDD: DW/BW was decreased obviously; HE staining revealed obvious changes in diaphragmatic tissue; Diaphragmatic contractility was also significantly decreased; The expression of Cyt c and caspase-3 were increased while the expression of RyR1 and p-mTORC1 were decreased gradually with the extension of treatment time ( P<0.05). Compared the EDP+VC group with the VC group, with the extension of treatment time, DW, DW/BW, pathological damages and diaphragmatic contractility were improved [PTD 1: (0.80±0.05)kg vs (0.56±0.04) kg, PTD 3: (1.06±0.05) kg vs (0.47±0.03) kg, PTD 7: (1.24±0.10) kg vs (0.39±0.07) kg, all P<0.05; PTD 1: (2.05±0.54) vs (1.86±0.72), PTD 3: (2.19±0.61) vs (1.74±0.40), PTD 7: (2.46±0.62) vs (1.53±0.85), all P<0.05; PTD 1: (2.39±0.42) N/cm 2vs (1.91±0.25) N/cm 2, PTD 3: (2.57±0.62) N/cm 2vs (1.72±0.50) N/cm 2, PTD 7: (2.77±0.55) N/cm 2vs (1.54±0.33) N/cm 2, all P<0.05]. The expression of Cyt c and caspase-3 were decreased while the expression of RyR1 and p-mTORC1 were increased gradually in the EDP+VC group ( P<0.05). Conclusions:External diaphragm pacer plays a protective role in ventilator-induced diaphragm dysfunction, which can inhibit mitochondrial damage, reduce oxidative damage, and mitigate diaphragmatic atrophy and injury.
RESUMO
Objective:To explore the change of blood-brain barrier (BBB) permeability in septic rats.Methods:A rat model of sepsis was established by cecal ligation and puncture. Rats were randomly (random number) grouped according to the intervention time: sham-operated group, sepsis 1-day group, sepsis 4-day group, and sepsis 7-day group. Fluorescein sodium was used to test the permeability of the BBB. Western blot and immunofluorescence methods were applied to detect the expression of tight junction proteins including Claudin-5, Occludin and ZO-1.Results:Compared with the sham-operated group, rats in the sepsis group presented quick breath, slow response, decreased intake of food and water, obvious abdominal distension and loose stools. After abdominal anatomy of sepsis rats, we found mesenteric adhesions, dilatation of proximal intestinal, black cecum ligation site with purulent exudate, enlarged liver and diffused bloody exudate. Compared with the sham-operated group, body weight of sepsis rats was reduced remarkably ( P < 0.05). The body weight of rats of sepsis 7-day group was the lowest, which was significantly lower than that of rats of sepsis 4-day group ( P< 0.05) and 1-day group ( P< 0.05). Compared with the sham-operated group, the content of fluorescein sodium in sepsis 1-day rats was increased remarkably ( P< 0.05). The content of fluorescein sodium in rats of sepsis 7-day group was the highest, which was significantly higher than that in rats of sepsis 4-day group ( P< 0.05) and 1-day group ( P< 0.05). Compared with the sham-operated rats, the expression of Claudin-5, Occludin and ZO-1 in sepsis rats were decreased remarkably (all P < 0.05). The expression of Claudin-5, Occludin and ZO-1 were the lowest in rats of the sepsis 7-day group, which were significantly decreased than those of rats in the sepsis 4-day group (all P< 0.05) and rats in sepsis 1-day group (all P < 0.05). Conclusions:Sepsis rats showed increased permeability of the BBB, and the permeability of BBB increased continuously along with the duration of sepsis.
RESUMO
Objective:To explore the mechanism of resveratrol on ameliorating the cognitive dysfunction induced by sepsis associated encephalopathy (SAE) in rats.Methods:The 12 weeks old male Sprague-dawley (SD) male rats were randomly divided into sham group, sepsis group and resveratrol group, with 30 rats in each group. The rat model of sepsis was made by injecting LPS (10 mg/kg) into tail vein. The rats in sham group was given the same amount of normal saline (NS). After LPS injection, resveratrol (8 mg·kg -1·d -1) was intraperitoneally injected once daily for 2 days in the resveratrol group; the same amount of NS was given to the sepsis group and sham group. At 24 hours after model establishment, the cognitive function of the experimental rats was assessed by the Morris water maze test. The blood-brain barrier (BBB) permeability was evaluated by the brain water content (BWC) and Evans blue (EB) test. The protein expressions of matrix metalloproteinase 9 (MMP-9), Occludin and Claudin-5 in cortical tissue were detected by Western Blot. Double immunofluorescence was used to verify the co-localization of MMP-9 protein and the marker protein of astrocyte GFAP in the cortical tissue of rats. Results:Compared with the sham group, the escape latency in the sepsis group was significantly longer [48-hour escape latency (s): 56.56±6.43 vs. 36.62±3.32, 72-hour escape latency (s): 57.72±7.23 vs. 26.46±4.24, both P < 0.01], the BWC and extravasation of EB were increased [BWC: (84.56±2.03)% vs. (76.82±2.22)%, EB (μg/g): 17.56±2.28 vs. 6.25±1.36, both P < 0.01], the expression of MMP-9 protein was increased (MMP-9/β-actin: 0.73±0.01 vs. 0.24±0.01, P < 0.01), the protein expressions of Occludin and Claudin-5 were decreased (Occludin/β-actin: 0.45±0.02 vs. 0.86±0.04, Claudin-5/β-actin: 0.62±0.03 vs. 0.96±0.05, both P < 0.01). At the same time, the co-localization expression of MMP-9 protein and the astrocytes of the cortical were increased [MMP-9 fluorescence intensity (AU): 38.66±4.26 vs. 17.23±3.04, MMP-9 positive cells: (26.92±1.77)% vs. (12.82±1.46)%, both P < 0.01]. Compared with the sepsis group, the escape latency in resveratrol group was significantly shorter [48-hour escape latency (s): 41.42±6.27 vs. 56.56±6.43, 72-hour escape latency (s): 33.46±7.17 vs. 57.72±7.23, both P < 0.01], the BWC and extravasation of EB were decreased [BWC: (77.15±2.27)% vs. (84.56±2.03)%, EB (μg/g): 7.74±1.88 vs. 17.56±2.28, both P < 0.01], the expression of MMP-9 protein was decreased (MMP-9/β-actin: 0.25±0.01 vs. 0.73±0.01, P < 0.01), the protein expressions of Occludin and Claudin-5 were increased (Occludin/β-actin: 0.82±0.03 vs. 0.45±0.02, Claudin-5/β-actin: 0.92±0.04 vs. 0.62±0.03, both P < 0.01). At the same time, the co-localization expression of MMP-9 protein and the astrocytes of the cortical were decreased [MMP-9 fluorescence intensity (AU): 19.44±4.37 vs. 38.66±4.26, MMP-9 positive cells: (13.11±1.29)% vs. (26.92±1.77)%, both P < 0.01]. Conclusion:Resveratrol can inhibit the expression of MMP-9 protein in the astrocytes of the cortical cortex of rats, and then reduce the degradation of tight junction proteins of Occludin and Claudin-5, thereby reducing BBB permeability and eventually ameliorate the cognitive dysfunction induced by SAE.
RESUMO
Objective:To investigate the effect of hypercapnia at admission on the clinical prognosis and the severity of infection in patients with severe community-acquired pneumonia (SCAP).Methods:The clinical data of 219 SCAP patients admitted to the department of emergency & critical care medicine of Guangdong Provincial People's Hospital from December 2017 to November 2019 were retrospectively analyzed. Based on the partial pressure of arterial carbon dioxide (PaCO 2) within 1 day after admission, the patients were divided into hypocapnia group [HO group, PaCO 2 < 35 mmHg (1 mmHg = 0.133 kPa)], normal carbonation group (NC group, PaCO 2 35-45 mmHg) and hypercapnia group (HC group, PaCO 2 > 45 mmHg). The clinical parameters of patients, such as gender, age, underlying diseases, white blood cell (WBC), procalcitonin (PCT), C-reactive protein (CRP), interleukin-6 (IL-6), pH value and lactate (Lac) within 1 day after admission were reviewed. The oxygenation index (PaO 2/FiO 2), pneumonia severity index (PSI) score and acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ) score were evaluated. The change tendencies of each index on day 1, day 3, and day 5 after admission were observed subsequently. Meanwhile, the rate of invasive mechanical ventilation (IMV), length of hospital stays and 28-day mortality among three groups were compared. Kaplan-Meier survival analysis was performed to assess the 28-day cumulative survival rate of patients with SCAP among three groups. Multivariate Logistic regression analysis was used to screen the risk factors of IMV and 28-day death in patients with SCAP. Results:Compared with the HO group ( n = 68) and NC group ( n = 72), the HC group ( n = 79) had higher proportion of preexisting comorbid chronic obstructive pulmonary disease (COPD) and PSI score, lower PCT, CRP, IL-6, and pH values. Compared with the HO group and NC group, there were smaller improvement trends on the levels of WBC, PCT, CRP, IL-6, PaO 2/FiO 2 and Lac at day 3 and day 5 as compared with day 1 in the HC group. On the 5th day after admission, the levels of WBC, PCT, CRP, IL-6, and Lac in the HC group were significantly higher than those in the HO group and NC group [WBC (×10 9/L): 18.33±1.44 vs. 10.89±2.37, 11.15±1.74; PCT (μg/L): 5.04±1.18 vs. 3.46±0.87, 3.58±0.83; CRP (mg/L): 78.43±7.17 vs. 54.24±4.97, 57.93±5.39; IL-6 (ng/L): 75.35±11.92 vs. 60.11±10.27, 57.88±12.34; Lac (mmol/L): 4.36±1.24 vs. 0.78±0.39, 0.86±0.64; all P < 0.01], and the lowest in PaO 2/FiO 2 was found in the HC group as compared with the HO and NC groups (mmHg: 171.31±6.73 vs. 226.68±7.36, 225.93±6.92, both P < 0.01). Compared with the HO group and NC group, the HC group had highest proportion of IMV (29.1% vs. 22.1%, 22.2%, both P < 0.01) and 28-day mortality (26.6% vs. 13.2%, 13.9%, both P < 0.01). Even when the patients with COPD were excluded from the analysis, the differences persisted among the groups. Kaplan-Meier survival analysis suggested that HC group had a higher 28-day cumulative survival rate as compared with the HO and NC groups (Log-Rank test: χ 12 = 4.976, P1 = 0.026; χ 22 = 4.629, P2 = 0.031). Multivariate Logistic regression analysis showed that IL-6, PSI score and hypercapnia within 1 day and PCT on the 5th day after admission were the independent risk factors of requiring IMV and 28-day death in patients with SCAP [odds ratio ( OR) were 0.325, 1.229, 1.396, 1.313, respectively, all P < 0.01]. Even when patients with COPD were excluded from the analysis, the above results had not been changed. Conclusion:Hypercapnia at admission was associated with higher proportion of IMV and 28-day mortality in patients with SCAP, which may be related to its early suppression of inflammation and then increment of infection.
RESUMO
Objective? To?explore?whether?β1?receptor?blocker?could?decrease?the?myocardial?inflammation??through?the?Toll-like?receptor?4/nuclear?factor-κB?(TLR4/NF-κB)?signaling?pathway?in?the?sepsis?adult?rats.? Methods? ?Sixty?male?Wistar?rats?(250-300?g)?aged?3?months?old?were?allocated?to?four?groups?by?random?number?table?(n?=?15):?sham?operation?group?(S?group),?sepsis?model?group?(CLP?group),?β1?receptor?blocker?esmolol?intervention?group??(ES?group),?and?inhibitor?of?the?TLR4?E5564?intervention?group?(E5564?group).?The?rat?sepsis?model?was?established?by?cecal?ligation?and?puncture?(CLP);?S?group?of?rats?underwent?only?an?incision.?Rats?in?S?group,?CLP?group?and?E5564?group?were?subcutaneous?injected?with?0.9%?sodium?chloride?(NaCl)?2.0?mL/kg.?Besides,?the?rats?in?ES?group?were?injected?with?esmolol?(15?mg·kg-1·h-1)?by?micro?pump?through?the?caudal?vein.?The?rats?in?E5564?group?were?injected?with?E5564?(0.3?mg·kg-1·h-1)?by?micro?pump?through?the?caudal?vein?1?hour?before?the?CLP?surgery.?Samples?were?collected?6?hours?after?the?modelling?in?each?group.?The?average?arterial?pressure?(MAP)?and?cardiac?output?index?(CI)?were?monitored?by?PU?electrical?conduction?ECG?monitor.?The?levels?of?serum?cardiac?troponin?I?(cTnI),?interleukin-1β?? (IL-1β)?and?tumor?necrosis?factor-α(TNF-α)?were?detected?by?enzyme?linked?immunosorbent?assay?(ELISA).?The?expressions?of?TLR4,?NF-κB?p65,?IL-1β,?TNF-α?in?myocardial?tissue?was?detected?by?Western?Blot.? Results? There?was?no?significant?difference?in?MAP?in?each?group.?Compared?with?the?S?group,?the?CI?in?the?CLP?group?was?significantly?decreased,?the?levels?of?serum?cTnI,?IL-1β,?TNF-α?were?significantly?increased,?the?protein?expressions?of?myocardial?tissue?TLR4,?NF-κB?p65,?IL-1β?and?TNF-α?were?significantly?increased.?Compared?with?the?CLP?group,?the?CI?in?the?ES?group?and?E5564?group?were?significantly?increased?(mL·s-1·m-2:?58.6±4.3,?58.9±4.4?vs.?41.2±3.9,?both?P?<?0.01),?the?levels?of?serum?cTnI,?IL-1β?and?TNF-α?were?significantly?decreased?[cTnI?(μg/L):?1?113.81±26.64,?1?115.74±25.90?vs.?1?975.96±42.74;?IL-1β(ng/L):?39.6±4.3,?38.9±4.4?vs.?61.2±3.9;?TNF-α?(ng/L):?43.1±2.8,?48.7±2.6?vs.?81.3±4.4,?all?P?<?0.01],?the?protein?expressions?of?myocardial?tissue?NF-κB?p65,?IL-1β,??TNF-αwere?significantly?decreased?(NF-κB?p65/β-actin:?0.31±0.03,?0.43±0.04?vs.?0.85±0.08;?IL-1β/β-actin:?0.28±0.05,?0.32±0.03?vs.?0.71±0.06;?TNF-α/β-actin:?0.18±0.04,?0.28±0.03?vs.?0.78±0.07,?all?P?<?0.01),?but?there?was?no?significant?difference?in?protein?expression?of?TLR4?(TLR4/β-actin:?0.89±0.07,?0.87±0.09?vs.?0.95±0.09,?both?P?>?0.05).?There?was?no?significant?difference?in?CI,?the?levels?of?serum?cTnI,?IL-1β,?TNF-α,?and?the?protein?expressions?of?myocardial?tissue?TLR4,?NF-κB?p65,?IL-1β,?TNF-αbetween?ES?group?and?E5564?group?(all?P?>??0.05).? Conclusion? β1?receptor?blocker?esmolol?may?inhibit?myocardial?inflammatory?response?in?sepsis?adult?rats?through?TLR4/NF-κB?signaling?pathway,?thereby?alleviating?sepsis-induced?myocardial?injury.
RESUMO
Objective@#This study aimed to explore whether high pressure would increase expression of TNF-a and IL-1β.@*Methods@#BV2 microglia cells were treated with a self-made device. BV2 microglia cells were randomly divided into five groups according to different pressures: control group, 20 mmHg group, 25 mmHg group, 30 mmHg group, and 35 mmHg group. BV2 microglia cells were randomly divided into five groups according to different intervention time: control group, 6 h group, 12 h group, 24 h group. TNF-α and IL-1β expression were assessed by Western Blotting or double immunofluorescence.@*Results@#The 30 mmHg group had the highest expression levels of TNF-α and IL-1β as compared with control group (both P<0.01), 6 h group (both P<0.01)、12 h group (TNF-α: P<0.05; IL-1β: P< 0.01).30 mmHg group had the highest expression levels of TNF-α and IL-1β as compared with control group (bothP<0.01), 20 mmHg group (both P<0.01), and 25 mmHg group (TNF-α: P<0.05; IL-1β: P<0.01). The expression levels of TNF-α and L-1β were not different between 30 mmHg group and 35 mmHg group (both P>0.05).@*Conclusions@#High pressure may increase the expression levels of TNF-α and IL-1β of microglia.
RESUMO
Objective@#To examine whether presepsin level can serve as a distinguishing marker between G- bacteria and G+ bacteria, fungal infection in sepsis patients.@*Methods@#A prospective observation study was conducted on the consecutive patients with positive bacterial cultures in intensive care unit (ICU) from June 2017 to November 2018. The patients were divided into the G- group, G+ group and fungal group. Blood samples were collected upon admission to measure the levels of presepsin and procalcitonin (PCT).@*Results@#(1) Of the 156 patients met the inclusion criteria. 96 (62% G- rods, 25 (16%) G+ microbes, and 35 (22%) fungi were detected. (2) Presepsin concentrations were significantly higher in the G- group compared with the G+ and fungal groups (P = 0.000). (3) Presepsin level has a higher accuracy in differentiating G- sepsis from Gram+ and fungal sepsis than PCT level [area under the curve (AUC): 0.809 vs 0.712]. The AUC value of a combination of presepsin and PCT level was significantly larger than that of presepsin level alone in differentiating G- sepsis from Gram+ and fungal sepsis (AUC: 0.866 vs 0.809).@*Conclusions@#In contrast to PCT, presepsin is a good discriminative biomarker in different infections.
RESUMO
Objective To examine whether presepsin level can serve as a distinguishing marker between G-bacteria and G+ bacteria,fungal infection in sepsis patients.Methods A prospective observation study was conducted on the consecutive patients with positive bacterial cultures in intensive care unit (ICU) from June 2017 to November 2018.The patients were divided into the G-group,G+ group and fungal group.Blood samples were collected upon admission to measure the levels of presepsin and procalcitonin (PCT).Results (1) Of the 156 patients met the inclusion criteria.96 (62％ G-rods,25 (16％) G+ microbes,and 35 (22％) fungi were detected.(2) Presepsin concentrations were significantly higher in the G-group compared with the G+ and fungal groups (P =0.000).(3) Presepsin level has a higher accuracy in differentiating G-sepsis from Gram+ and fungal sepsis than PCT level [area under the curve (AUC):0.809 vs 0.712].The AUC value of a combination of presepsin and PCT level was significantly larger than that of presepsin level alone in differentiating G-sepsis from Gram+ and fungal sepsis (AUC:0.866 vs 0.809).Conclusions In contrast to PCT,presepsin is a good discriminative biomarker in different infections.
RESUMO
OBJECTIVE@#To explore whether β1 receptor blocker could decrease the myocardial inflammation through the Toll-like receptor 4/nuclear factor-ΚB (TLR4/NF-ΚB) signaling pathway in the sepsis adult rats.@*METHODS@#Sixty male Wistar rats (250-300 g) aged 3 months old were allocated to four groups by random number table (n = 15): sham operation group (S group), sepsis model group (CLP group), β1 receptor blocker esmolol intervention group (ES group), and inhibitor of the TLR4 E5564 intervention group (E5564 group). The rat sepsis model was established by cecal ligation and puncture (CLP); S group of rats underwent only an incision. Rats in S group, CLP group and E5564 group were subcutaneous injected with 0.9% sodium chloride (NaCl) 2.0 mL/kg. Besides, the rats in ES group were injected with esmolol (15 mg×kg-1×h-1) by micro pump through the caudal vein. The rats in E5564 group were injected with E5564 (0.3 mg×kg-1×h-1) by micro pump through the caudal vein 1 hour before the CLP surgery. Samples were collected 6 hours after the modelling in each group. The average arterial pressure (MAP) and cardiac output index (CI) were monitored by PU electrical conduction ECG monitor. The levels of serum cardiac troponin I (cTnI), interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) were detected by enzyme linked immunosorbent assay (ELISA). The expressions of TLR4, NF-ΚB p65, IL-1β, TNF-α in myocardial tissue was detected by Western Blot.@*RESULTS@#There was no significant difference in MAP in each group. Compared with the S group, the CI in the CLP group was significantly decreased, the levels of serum cTnI, IL-1β, TNF-α were significantly increased, the protein expressions of myocardial tissue TLR4, NF-ΚB p65, IL-1β and TNF-α were significantly increased. Compared with the CLP group, the CI in the ES group and E5564 group were significantly increased (mL×s-1×m-2: 58.6±4.3, 58.9±4.4 vs. 41.2±3.9, both P < 0.01), the levels of serum cTnI, IL-1β and TNF-α were significantly decreased [cTnI (μg/L): 1 113.81±26.64, 1 115.74±25.90 vs. 1 975.96±42.74; IL-1β (ng/L): 39.6±4.3, 38.9±4.4 vs. 61.2±3.9; TNF-α (ng/L): 43.1±2.8, 48.7±2.6 vs. 81.3±4.4, all P < 0.01], the protein expressions of myocardial tissue NF-ΚB p65, IL-1β, TNF-α were significantly decreased (NF-ΚB p65/β-actin: 0.31±0.03, 0.43±0.04 vs. 0.85±0.08; IL-1β/β-actin: 0.28±0.05, 0.32±0.03 vs. 0.71±0.06; TNF-α/β-actin: 0.18±0.04, 0.28±0.03 vs. 0.78±0.07, all P < 0.01), but there was no significant difference in protein expression of TLR4 (TLR4/β-actin: 0.89±0.07, 0.87±0.09 vs. 0.95±0.09, both P > 0.05). There was no significant difference in CI, the levels of serum cTnI, IL-1β, TNF-α, and the protein expressions of myocardial tissue TLR4, NF-ΚB p65, IL-1β, TNF-α between ES group and E5564 group (all P > 0.05).@*CONCLUSIONS@#β1 receptor blocker esmolol may inhibit myocardial inflammatory response in sepsis adult rats through TLR4/NF-ΚB signaling pathway, thereby alleviating sepsis-induced myocardial injury.
Assuntos
Animais , Masculino , Ratos , Inflamação/prevenção & controle , Interleucina-1beta , Miocárdio/patologia , NF-kappa B/metabolismo , Propanolaminas/farmacologia , Ratos Wistar , Sepse/tratamento farmacológico , Transdução de Sinais/efeitos dos fármacos , Receptor 4 Toll-Like/metabolismo , Fator de Necrose Tumoral alfaRESUMO
Objective This study aimed to explore whether high pressure would increase expression of TNF-α and IL-1β.Methods BV2 microglia cells were treated with a self-made device.BV2 microglia cells were randomly divided into five groups according to different pressures: control group,20 mmHg group,25 mmHg group,30 mmHg group,and 35 mmHg group.BV2 microglia cells were randomly divided into five groups according to different intervention time: control group,6 h group,12 h group,24 h group.TNF-α and IL-1β expression were assessed by Western Blotting or double immunofluorescence.Results the 30 mmHg group had the highest expression levels of TNF-αand IL-1β as compared with control group(both P＜O.O1),6 h group(both P＜O.O1)、12h group(TNF-α: P＜0.05; IL-1β: P＜ 0.01).30 mmHg group had the highest expression levels of TNF-α and IL-1β as compared with control group(both P＜O.01),20 mmHg group(both P＜O.01),and 25 mmHg group(TNF-α P＜0.05; IL-1β: P＜O.01).The expression levels of TNF-α and L-1β were not different between 30 mmHg group and 35 mmHg group(both P＞0.05).Conclusions High pressure may increase the expression levels of TNF-α and IL-1β of microglia.
RESUMO
Objective To determine the effect of high dose albumin on permeability of blood brain barrier (BBB) in brain of rats after ischemic-reperfusion (IR) in order to explore its possible mechanism.Methods Establishment of brain ischemic reperfusion rat model by using middle cerebral artery occlusion (MCAO).Medicine treatment was given by caudal vein injection after 2 hours of MCAO.Thirty-six healthy male SD rats were then randomly (random number) divided into 6 groups (n =6 in each):6 h and 24 h sham-operation groups (Group Sham:operation without ischemia),6 h and 24 h normal saline groups (Group NS:NS injection 5 ml/kg) and 6 h and 24 h albumin group (Group Alb:25 ％ Alb injection 1.25 g/kg).Six hours and 24 hours after the end of reperfusion,rats were measured by Zea-Longa score (neural function deficit) separately.Serum concentration of S100B was examined by the ELISA kit and Evans blue in brain tissue was detected by spectrophotometer.The level of AQP4 was examined by Western blot and immunohistochemistry.All data were analyzed by one-way analysis of variance (ANOVA),The intergroup comparisons were analyzed by the least-significant-difference (LSD) test by using SPSS version 17.0 software.Differences were considered statistically significant if P ＜ 0.05.Results Zea-Longa score significantly increased in both group NS and group Alb at 6 h and 24 h (P =0.000).However,there was no significant difference in ZEA-LONGA score of 6 h and 24 h between group Alb and group NS (P =1.000).The serum concentration of S100B in group NS 6 h was significantly lower than that in group Alb at 6h (196.67±20.11 vs 160.04±14.00,P=0.000),and at24h (2.45±0.07 vs.2.23±0.07,P=0.000).Furthermore,concentration of Evans blue in brain tissue in group Alb was significantly higher than that in group NS at both 6 h (0.97 ± 0.08 vs.0.74 ± 0.06,P =0.000) and 24 h (2.45 ± 0.07 vs.2.23 ± 0.07,P =0.000).The expression of AQP4 in brain tissue was higher in group Alb than that in group NS at both 6 h (0.72 ±.0.11 vs.0.57 ± 0.06,P ＜ 0.01) and 24 h (0.80 ± 0.03 vs 0.61 ± 0.02,P ＜0.01).Conclusions High dose albumin contribute slightly in improvement of neural deficit in rats after IR.On the contrary,it can also aggravate the IR injury,which increases brain edema then increase the permeability of BBB.The mechanism may be associated with over-expression of AQP4 in brain tissue.
RESUMO
Objective To investigate microbial characteristics and predisposing factors in gram-negtive bacteria blood stream infection. Methods A descriptive retrospective study was conducted. Patients diagnosed as sepsis with blood culture of G- bacilli and without sepsis were enrolled. The patients were all admitted to ICUs of Guangdong General Hospital from October, 2012 to December, 2014. The clinical characteristics and outcomes were compared. Multiple logistic regression was used to analyse the predisposing factors for sepsis of G- bacilli. Results A total of 148 patients suffered from sepsis of G-bacilli including Acinetobacter baumannii, Escherichia coli and Klebsiella pneumoniae were enrolled. Single-factor analysis showed that patients with sepsis of G- bacilli infection had older ages, higher incidence of coronary heart diseases or congestive heart failure, cerebrovascular diseases or chronic renal insufficiency, hypertension, also higher incidence of longer length of hospital stay before blood was drawn for culture, and higher incidence using of vasoactive agents and pre-admission intravenous antibiotics and lower plasma albumin level (P < 0.05). Conclusions Coronary heart disease or congestive heart failure, chronic renal insufficiency and pre-admission intravenous antibiotics were independent predisposing factors for sepsis of G-bacilli.
RESUMO
Objective To evaluate (1,3)-β-D-glucan (BG) assay as an aid for invasive fungal infection (IFI) diagnosis in severe pneumonia patients (diagnosis followed 2007 American Thoracic Society (ATS) and Infectious Disease Society of America (IDSA) severe pneumonia standard).Methods BG antigenemia was measured by BG Assay Box.IFIs was classified according to the blood fungal laboratory reports.Results 558 patients (185 females,373 males,mean age 64.7) were included.41 patients were proven to be fungal infected to be classified in exposure group.BG assay mean value in exposure group and unexposure group were (568.53 ±796.57) pg/mL,(51.4 ±63.27) pg/mL,respectively.Patients in the exposure group had significantly higher BG assay value than patients in the unexposure group (P ＜0.05).For the cutoff 100 pg/mL recommended by manufacturer,the sensitivity,specificity,positive predict value and negative predict value of the BG assay were 92.7％,92.5％,49.4％ and 0.6％,respectively.Conclusion BG assay has positive clinical value in invasive fungal infection diagnosis in severe pneumonia patients.
RESUMO
Objective To evaluate the clinical efficacy of noninvasive positive pressure ventilation (NPPV) in the treatment of patients with acute respiratory distress syndrome (ARDS), and to look for the predictors of failure of NPPV. Methods A retrospective observation was conducted. ARDS patients underwent NPPV admitted to emergency intensive care unit (EICU) of Guangdong General Hospital from January 2013 to December 2015 were enrolled. The patients were divided into success group and failure group according to the clinical efficacy. The condition of the patients in the two groups was evaluated, and ARDS classification and acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ) score before treatment were recorded. Etiological composition of ARDS was analyzed. The parameters, including heart rate (HR), respiratory rate (RR), oxygenation index (PaO2/FiO2), arterial partial pressure of oxygen (PaO2), arterial partial pressure of carbon dioxide (PaCO2) and arterial oxygen saturation (SaO2), were recorded before and 2 hours after the treatment of NPPV. Multivariate logistic regression analysis was conducted for predicting the independent factors inducing the failure of NPPV treatment of patients with ARDS. Results The date of 137 patients with ARDS were collected, excluding the followed patients, 6 with coma, 18 with hemodynamic instability, 5 with severe hypoxia, and 5 with incomplete date. Finally, a total of 103 patients entered the statistics. There were 69 patients in NPPV success group, and 34 in failure group. Compared with success group, APACHE Ⅱ score in the failure group was higher (21.4±6.2 vs. 19.7±8.9), the ratios of patients with severe ARDS and those induced by pulmonary infection were higher [82.4% (28/34) vs. 5.8% (4/69), 32.4% (11/34) vs. 8.7% (6/69), respectively, both P < 0.05]. HR and RR before NPPV in the failure group were significantly higher than those of success group [HR (bpm): 124±13 vs. 117±12, RR (bpm): 39±5 vs. 33±4], and PaO2/FiO2, PaO2, PaCO2, and SaO2 were significantly lower than those of the success group [PaO2/FiO2 (mmHg, 1 mmHg = 0.133 kPa): 104±10 vs. 156±12, PaO2 (mmHg): 53±8 vs. 68±7, PaCO2 (mmHg): 31±5 vs. 37±7, SaO2: 0.83±0.07 vs. 0.91±0.05, all P < 0.05]. It was shown by logistic regression analysis that severe ARDS [odds ratio (OR) = 10.533, 95% confidence interval (95%CI) = 5.847-89.852, P = 0.000], pulmonary infection resulted ARDS (OR = 4.831, 95%CI = 1.688-13.825, P = 0.003) and PaO2/FiO2 < 140 mmHg 2 hours after treatment (OR = 7.049, 95%CI = 1.266-39.236, P = 0.026) were the independent risk factors of NPPV failure for the treatment of patients with ARDS. Conclusions Patients with severe ARDS and pulmonary infection derived ARDS were the risk factors of failure to NPPV in ARDS. Lack of improvement in oxygenation 2 hours after NPPV is the predictor of NPPV failure and change to invasive ventilation.
RESUMO
Objective To investigate the effects of stress hyperglycemia on prognosis in patients with severe cerebral vascular diseases.Methods A retrospective analysis was conducted.416 patients with severe cerebral vascular diseases confirmed by radiological imaging admitted to intensive care unit (ICU) of Guangdong General Hospital from December 2013 to June 2015 were enrolled.According to the values of randomise blood glucose (RBG) and glycosylated hemoglobin (HbA1c) and diabetes history,the patients were divided into euglycemia group (RBG ＜ 11.1 mmol/L,HbA1c ＜ 0.065,without diabetes history),diabetes group (RBG ≥ 11.1 mmol/L,HbA1c ≥ 0.065,with diabetes history),and stress hyperglycemia group (RBG ≥ 11.1 mmol/L,HbA1c ＜ 0.065,without diabetes history).The nosocomial infection rate,the length of ICU stay and 28-day mortality were compared among the three groups.Survival analysis was performed using Kaplan-Meier method,and multivariate Cox proportional hazard model was used to estimate the risk of death.Results Among 416 patients,there were 40 cases with stress hyperglycemia,46 with diabetes and 330 with euglycemia,with the incidence of stress hyperglycemia of 10.81％ (40/370).The nosocomial infection rates in the stress hyperglycemia group and diabetes group were significantly higher than those of the euglycemia group [55.00％ (22/40),52.17％ (24/46) vs.18.79％ (62/330),both P ＜ 0.01],and the length of ICU stay was significantly longer than that of the euglycemia group (days:16.53 ± 6.26,15.79 ± 8.51 vs.9.23 ± 4.29,both P ＜ 0.01).No significant differences in nosocomial intection rate and length of ICU stay were found between stress hyperglycemia group and diabetes group (both P ＞ 0.05).The 28-day mortality rate in stress hyperglycemia group was significantly higher than that of diabetes group and euglycemia group [47.50％ (19/40) vs.26.09％ (12/46),10.30％ (34/330),P ＜ 0.05 and P ＜ 0.01].It was showed by Kaplan-Meier survival analysis that 28-day cumulative survival rate in stress hyperglycemia group was significantly lower than that of euglycemia group and diabetes group (log-rank =6.148,P =0.043).It was showed by Cox death risk analysis that stress hyperglycemia was the risk factor of death in patients with severe cerebral vascular disease [hazard ratio (HR) =1.53,95％ confidence interval (95％CI) =1.04-1.26,P =0.001].Conclusion The patients with stress hyperglycemia may have a higher 28-day mortality and a poorer prognosis compared with those with diabetes and normal blood glucose in severe cerebral vascular diseases.
RESUMO
Objective To explore whether hypertonic saline would partake in regulating Notch signaling in microglia in experimentally induced cerebral ischemic rats.Methods Male SD rats were randomly divided into sham group, cerebral ischemia group, normal saline group ( NS group ) , 10%hypertonic saline group (10%HS group) , the model of cerebral ischemia were established in all rats except the sham group by using middle cerebral artery occlusion ( MCAO) .After 2 hours of MCAO, the rats were through reperfusion for 24 h.In addition, rats in the normal saline group and 10% HS group were respectively treated with a continuous intravenous injection of normal saline (0.3 mL/h) and 10%HS (0.3 mL/h) by tail vein for 24 h.Immunofluorescence methods, RT-PCR and Western blot were used to detect the expression of Notch1 and intracellular Notch receptor domain ( NICD) .All data was analyzed by one-way analysis of variance ( ANOVA) , The intergroup comparisons were analyzed by the least-significant-difference (LSD) tests.Differences were considered statistically significant if P<0.05.Results Immunofluorescence showed that the expression of Notch1 and NICD were significantly increased in the microglia around peri-ischemia area in cerebral ischemia group and normal saline group compared to sham group;the expression of Notch1 and NICD in the microglia around peri-ischemia area were significantly reduced in 10% HS group compared to ischemia group and NS group.RT-PCR showed that the mRNA expression of Notch1 was significantly increased in ischemia group and NS group compared to sham group ( sham group: 1.000 ± 0.076; ischemia group: 2.203 ±0.283; NS group: 1.616 ±0.185; P <0.01 ); however, it was significantly reduced in 10% HS group compared to ischemia group and NS group ( ischemia group:2.203 ±0.283; NS group: 1.616 ±0.185; 10%HS group: 1.202 ±0.177; P <0.05 ) .Western blot showed that the protein expression of Notch1 was significantly increased in ischemia group and NS group compared to sham group ( sham group: 0.290 ±0.079; ischemia group: 0.750 ±0.029; NS group:0.765 ±0.182;P<0.01);but was significantly reduced in 10%HS group compared to ischemia group and NS group ( ischemia group:0.750 ±0.029; NS group:0.765 ±0.182;10%HS group:0.390 ±0.195;P<0.05 ) .The protein expression of NICD was significantly increased in ischemia group and NS group compared to sham group ( sham group: 0.401 ±0.196; ischemia group: 0.906 ±0.359; NS group:0.847 ±0.153;P<0.01);but was significantly reduced in 10%HS group compared to ischemia group and NS group ( ischemia group:0.906 ±0.359; NS group:0.847 ±0.153;10%HS group:0.561 ±0.165;P<0.05 ) .Conclusion Our results suggest that HS markedly suppresses Notch signaling in microglia around the ischemia tissue area in experimental induced cerebral ischemic rats.
RESUMO
Objective To explore the advantages and disadvantages of helicopter emergency medical services of South China in the long-distance transport for critical patients.Methods A total of 30 patients who received helicopter emergency medical services by Guangdong Generral Hospital from August 2004 to December 2014 were selected as the observation group,and the other 30 patients with similar conditions who received ground emergency medical services were selected as the control group.To analyses the difference between the two groups in the disease,transport distance,transportation time,costs and compliction by χ2-test,t-test and nonparametric test according types of data.Results There were significantly difference between two groups in transport distances (km) [578.0 (313.0,707.5)vs.214.5 (101.5,313.5),P 0.05).Conclusions Helicopter emergency medical services could shorten the transportation time of critical patients on long distance transportation,and improve the efficiency of first-aid.However,there were many disadvantages that need to be improved in the helicopter emergency medical service of China.
RESUMO
OBJECTIVE: To investigate the clinical characteristics and pathogenic microorganisms in culture-positive sepsis, to identify its risk factors, and evaluate the prognosis on polymicrobial infection in intensive care unit (ICU). METHODS: A descriptive retrospective study was conducted. Clinical data of patients aged ≥ 18 years, diagnosed as culture-positive sepsis, and admitted to six ICUs of Guangdong General Hospital from October 12th, 2012 to December 1st, 2014 were enrolled. Based on the number of isolated pathogens, patients were divided into polymicrobial infection group (≥ two pathogens) and monomicrobial infection group (one pathogen) to investigate the clinical characteristics of patients with culture-positive sepsis and the causative pathogens. Multiple logistic regression was conducted to identify the risk factors for polymicrobial infection. Kaplan-Meier curve was plotted to analyze a 90-day survival rate from the onset of positive blood culture. RESULTS: 299 patients with positive blood culture were enrolled. A total of 450 strains of pathogens were isolated including 246 gram-positive cocci (54.67%), 167 gram-negative bacilli (37.11%) and 37 fungi (8.22%). Ninety-one patients had polymicrobial infection, and 208 with monomicrobial infection. Compared with monomicrobial infection group, patients suffering from polymicrobial infection had more advanced age (years: 73.19 ± 18.02 vs. 60.83 ± 18.06, t = -5.447, P = 0.000), also with higher incidence of cerebrovascular diseases [39.56% (36/91) vs. 17.79% (37/208), χ2 = 16.261, P = 0.000] or chronic renal insufficiency [15.38% (14/91) vs. 7.21% (15/208), χ2 = 4.828, P = 0.028], higher incidence of recent hospital stay (≥ 2 days) within 90 days [73.63% (67/91) vs. 61.54% (128/208), χ2 = 4.078, P = 0.043], longer mechanical ventilation duration [days: 4 (0, 17) vs. 1 (0, 6), U = 7673.000, P = 0.006], longer length of hospital stay before blood was drawn for culture [days: 21 (7, 40) vs. 9 (3, 17), U = 6 441.500, P = 0.006], and higher incidence of pre-admission intravenous use of antibiotics [84.62% (77/91) vs. 66.83% (139/208), χ2 = 9.989, P = 0.002]. Multiple logistic regression analysis showed that advanced age [odd ratio (OR) = 1.032, 95% confidential interval (95% CI) = 1.015-1.050, P = 0.000], cerebrovascular diseases (OR = 2.247, 95%CI = 1.234-4.090, P = 0.008), prolonged mechanical ventilation (OR = 1.041, 95% CI = 1.014-1.069, P = 0.003), and recent hospital stay (≥ 2 days) within 90 days (OR = 1.968, 95%CI = 1.079-3.592, P = 0.027) were the independent risk factors for polymicrobial infection. In the polymicrobial infection group, the length of ICU stay [days: 46 (22, 77) vs. 13 (7, 22), U = 3 148.000, P = 0.000] and hospital stay [days: 81 (47, 118) vs. 28 (17, 46), U = 3 620.000, P = 0.000] were significantly longer, and the ICU mortality [65.93% (60/91) vs. 43.75% (91/208), χ2 = 12.463, P = 0.000 ] and hospital mortality [68.13% (62/91) vs. 45.67% (95/208), χ2 = 12.804, P = 0.000] were significantly higher, and on the other hand the 90-day survival rate was significantly lower than that in the monomicrobial infection group (χ2 = 8.513, P = 0.004). CONCLUSIONS: The most common pathogen of ICU sepsis is gram-positive cocci. Independent risk factors for polymicrobial infections were found to be advanced age, occurrence of cerebrovascular disease, prolonged mechanical ventilation, and recent hospitalization. Polymicrobial infection is associated with longer length of ICU and hospital stay, as well as higher mortality.
