OBJECTIVES: To investigate the effect of high glucose on macrophage polarization and the role of immune-responsive gene 1 (IRG1) in mediating its effect. METHODS: RAW264.7 cells were transfected with IRG1-overexpressing plasmid or IRG1 siRNA via electroporation and cultured in either normal or high glucose for 72 h to observe the changes in cell viability and morphology using CCK-8 assay and phase contrast microscopy. The protein levels of IRG1, iNOS, Arg-1, IL-1β and IL-10 in the treated cells were detected with Western blotting, and the fluorescence intensities of iNOS and Arg-1 were detected using immunofluorescence assay. The protein levels of IL-1β and IL-10 in the culture medium were determined with ELISA. RESULTS: High glucose exposure significantly reduced IRG1 and Arg-1 expressions, increased iNOS and IL-1β expressions and IL-1β secretion, and decreased IL-10 level in RAW264.7 cells. Transfection with the IRG1-overexpressing plasmid provided the cells with obvious resistance to high glucose-induced changes in iNOS, Arg-1, IL-1β and IL-10, whereas IRG1 knockdown further enhanced the effects of high glucose exposure on Arg-1 expression and the expression and secretion of IL-10. CONCLUSIONS High glucose promotes M1 polarization of the macrophages possibly through a mechanism to inhibit the expression of IRG1 protein, thus leading to chronic inflammatory response.
Animals ; Mice ; Macrophages/drug effects* ; Glucose/pharmacology* ; Interleukin-10/metabolism* ; Nitric Oxide Synthase Type II/metabolism* ; RAW 264.7 Cells ; Interleukin-1beta/metabolism* ; Arginase/metabolism* ; RNA, Small Interfering/genetics* ; Transfection ; Inflammation

Objective To explore the regulatory effect of moderate intensity aerobic exercise on glu-cose and lipid metabolism disordersafter immune stimulation in high-fat diet induced insulin resistance(IR)mice by inducing tolerance of trained immunity.Methods Eighteen of 70 male C57BL/6 male mice were randomly selected as the control group(CON group),while the remaining mice were subjected to high-fat diet intervention(HFD group)for 8 weeks.After modeling,six of the CON group and HFD group were measured their glucose and lipid metabolism and inflammation levels.The remaining mice in the HFD group were randomly divided into HFD sedentary group(HS group)and HFD exer-cise group(HE group),each of 16.The HE groups underwent a daily 60-minute running on a hori-zontal treadmill at 12 m/min,5 days a week for 8 weeks.After that,the CON,HS and HE groups were randomly divided into an immune stimulation group(lipopolysaccharides,LPS group)and a con-trol group(phosphate buffered saline,PBS group),with 6 in CON-PBS and CON-LPS groups,and 8 in HS-PBS,HS-LPS,HE-PBS and HE-LPS groups.The LPS group received intraperitoneal injec-tion of LPS as an immune stimulus,and were taken samples 24 hours after intervention.During the intervention period,the body weight,food intake,fasting blood glucose(FBG),glucose tolerance,and insulin tolerance were tested for all groups.Then,the serum blood lipid level was tested.More-over,the levels of tumor necrosis factor-α(TNF-α),interleukin-1 β(IL-1β)and interleukin-10(IL-10)in serum were detected by using the enzyme-linked immunosorbent assay,while the protein expression of IL-1β,IL-10,induciblenitricoxidesynthase(iNOS)andarginase-1(Arg-1)were measured by using Western Blot.Results(1)After 8 weeks of high-fat diet intervention,compared with the CON group,there was a significant increase in the body weight,food intake,and FBG,the level of TNF-α and IL-1β in serum and expressions of IL-1β and iNOS in liver,skeletal muscle and adipose tissue,but a significant decrease in glucose and insulin tolerance,the level of anti-in-flammatory factor IL-10,as well as IL-10 and Arg-1 in liver and Arg-1 in adipose tissues in group HFD(P<0.01,P<0.05).(2)After 8 weeks of diet intervention,the body weight of group HS-PBS was still significantly higher than group CON-PBS(P<0.01).However,no significant differences were found between group CON-PBS and HS-PBS in other indicators(P>0.05).After LPS intervention,the food intake of both CON-LPS and HS-LPS groups was significantly lower than the corresponding PBS group(P<0.05).However,the levels of FBG,TG,TC,LDL-C,TNF-α and IL-1β in serum,IL-1β and iNOS in liver and adipose tissues,and iNOS in skeletal muscles of group HS-LPS were signif-icantly higher compared with group HS-PBS and CON-LPS(P<0.05).Meanwhile,the levels of IL-10 in serum,skeletal muscles and adipose tissues,and Arg-1 in skeletal muscles and adipose tissues of group HS-LPS decreased significantly compared with group HS-PBS and CON-LPS(P<0.05).(3)Af-ter simultaneous aerobic exercise intervention,there were no significant differences between group HE-LPS and HE-PBS in FBG,TC,LDL-C,TNF-α,IL-1β and IL-10 in serum,as well as IL-1β,iN-OS and IL-10 in the liver,skeletal muscles and adipose tissues(P>0.05).Moreover,thelevels of FBG,TG,TC,TNF-α,IL-1β in serum,and IL-1β and iNOS in the liver,skeletal muscle and adi-pose tissue decreased significantly in group HE-LPS compared with group HS-LPS(P<0.05).Howev-er,the levels of IL-10 in the serum and liver,and IL-10 and Arg-1 in skeletal muscles and adi-pose tissues increased significantly in group HE-LPS compared with group HS-LPS(P<0.05).Conclu-sion Eight-week aerobic exercise can effectively relieve the glucose and lipid metabolism disorder after immune stimulation in IR mice,which may be related to the stimulation of immunologic tolerance in innate immune cells,thereby reducing the excessive inflammatory response caused by secondary im-mune stimulation.

Objective To explore the regulatory effect of moderate intensity aerobic exercise on glu-cose and lipid metabolism disordersafter immune stimulation in high-fat diet induced insulin resistance(IR)mice by inducing tolerance of trained immunity.Methods Eighteen of 70 male C57BL/6 male mice were randomly selected as the control group(CON group),while the remaining mice were subjected to high-fat diet intervention(HFD group)for 8 weeks.After modeling,six of the CON group and HFD group were measured their glucose and lipid metabolism and inflammation levels.The remaining mice in the HFD group were randomly divided into HFD sedentary group(HS group)and HFD exer-cise group(HE group),each of 16.The HE groups underwent a daily 60-minute running on a hori-zontal treadmill at 12 m/min,5 days a week for 8 weeks.After that,the CON,HS and HE groups were randomly divided into an immune stimulation group(lipopolysaccharides,LPS group)and a con-trol group(phosphate buffered saline,PBS group),with 6 in CON-PBS and CON-LPS groups,and 8 in HS-PBS,HS-LPS,HE-PBS and HE-LPS groups.The LPS group received intraperitoneal injec-tion of LPS as an immune stimulus,and were taken samples 24 hours after intervention.During the intervention period,the body weight,food intake,fasting blood glucose(FBG),glucose tolerance,and insulin tolerance were tested for all groups.Then,the serum blood lipid level was tested.More-over,the levels of tumor necrosis factor-α(TNF-α),interleukin-1 β(IL-1β)and interleukin-10(IL-10)in serum were detected by using the enzyme-linked immunosorbent assay,while the protein expression of IL-1β,IL-10,induciblenitricoxidesynthase(iNOS)andarginase-1(Arg-1)were measured by using Western Blot.Results(1)After 8 weeks of high-fat diet intervention,compared with the CON group,there was a significant increase in the body weight,food intake,and FBG,the level of TNF-α and IL-1β in serum and expressions of IL-1β and iNOS in liver,skeletal muscle and adipose tissue,but a significant decrease in glucose and insulin tolerance,the level of anti-in-flammatory factor IL-10,as well as IL-10 and Arg-1 in liver and Arg-1 in adipose tissues in group HFD(P<0.01,P<0.05).(2)After 8 weeks of diet intervention,the body weight of group HS-PBS was still significantly higher than group CON-PBS(P<0.01).However,no significant differences were found between group CON-PBS and HS-PBS in other indicators(P>0.05).After LPS intervention,the food intake of both CON-LPS and HS-LPS groups was significantly lower than the corresponding PBS group(P<0.05).However,the levels of FBG,TG,TC,LDL-C,TNF-α and IL-1β in serum,IL-1β and iNOS in liver and adipose tissues,and iNOS in skeletal muscles of group HS-LPS were signif-icantly higher compared with group HS-PBS and CON-LPS(P<0.05).Meanwhile,the levels of IL-10 in serum,skeletal muscles and adipose tissues,and Arg-1 in skeletal muscles and adipose tissues of group HS-LPS decreased significantly compared with group HS-PBS and CON-LPS(P<0.05).(3)Af-ter simultaneous aerobic exercise intervention,there were no significant differences between group HE-LPS and HE-PBS in FBG,TC,LDL-C,TNF-α,IL-1β and IL-10 in serum,as well as IL-1β,iN-OS and IL-10 in the liver,skeletal muscles and adipose tissues(P>0.05).Moreover,thelevels of FBG,TG,TC,TNF-α,IL-1β in serum,and IL-1β and iNOS in the liver,skeletal muscle and adi-pose tissue decreased significantly in group HE-LPS compared with group HS-LPS(P<0.05).Howev-er,the levels of IL-10 in the serum and liver,and IL-10 and Arg-1 in skeletal muscles and adi-pose tissues increased significantly in group HE-LPS compared with group HS-LPS(P<0.05).Conclu-sion Eight-week aerobic exercise can effectively relieve the glucose and lipid metabolism disorder after immune stimulation in IR mice,which may be related to the stimulation of immunologic tolerance in innate immune cells,thereby reducing the excessive inflammatory response caused by secondary im-mune stimulation.

Objective:To explore the correlation between different types of microcirculation alterations and the prognosis in patients with septic shock.Methods:This research employed a prospective observational study methodology for selecting subjects with septic shock. Side-stream dark field(SDF) was used to monitor the sublingual microcirculation to determine the total vascular density (TVD), perfused vessel density (PVD), the proportion of perfused vessels (PPV), and the microvascular flow index (MFI), heterogeneity index (HI) indicators. At the bedside, patients with microcirculation disorders were divided into four types: stasis, dilution, heterogeneity, and hyperdynamic. The 30-day survival status after enrollment and hemodynamics parameters were recorded.Results:A total of 64 patients with septic shock were selected in the study, including 18 cases of stasis type, 11 of dilution type, 18 of heterogeneous type, and 17 of hyperdynamic type. There were statistical differences in the mean arterial pressure (MAP) [stasis:(77±9) mmHg (1 mmHg=0.133 kPa), dilution:(80±11) mmHg, heterogeneity: (78±12) mmHg, hyperdynamic:(88±12) mmHg], TVD [ stasis:(10.84±3.01) mm/mm 2, dilution:(9.64±1.72) mm/mm 2, heterogeneity:(11.39±2.18) mm/mm 2, hyperdynamic: (11.87±2.67) mm/mm 2 ], PVD [stasis:(5.93±1.94) mm/mm 2, dilution:(6.86±1.48) mm/mm 2, heterogeneity: (8.31±1.78) mm/mm 2, hyperdynamic:(9.68±2.46) mm/mm 2], PPV [stasis:52.45 (46.25, 63.33)%, dilution:73.70 (61.50, 75.20)%, heterogeneity: 71.25 (67.95, 77.00)%, hyperdynamic:80.70 (77.25, 86.45)%], MFI(stasis:1.34±0.45, dilution: 1.70±0.38, heterogeneity:1.82±0.28, hyperdynamic:2.25±0.33), and HI [stasis:0.68 (0.51, 1.87), dilution: 0.57 (0.49, 0.64), heterogeneity:0.70 (0.59, 0.91), hyperdynamic: 0.40 (0.37, 0.52)] of the four types of microcirculation alterations. The cumulative survival rates in stasis, dilution, heterogeneity and hyperdynamic types at 30 day were 7/18, 4/11, 10/18 and 14/17, respectively, which in stasis and dilution types was significantly lower than that of hyperdynamic type (χ2=7.221, P=0.007;χ 2=6.764, P=0.009). Multivariate Cox regression analysis showed the type of microcirculation alterations (stasis: RR=4.551, 95 %CI 1.228-16.864, P=0.023; dilution: RR=4.086, 95 %CI 1.011-16.503, P=0.048), acute physiology and chronic health evaluation Ⅱ ( RR=1.077, 95 %CI 1.006-1.153, P=0.032) were independent prognostic risk factors. Conclusions:Microcirculation alterations are common in patients with septic shock, and it is hard to predict the types of microcirculation alterations with hemodynamics parameters. The prognosis of patients with septic shock is related to the types of microcirculation alterations, suggesting that routine monitoring of microcirculation might be helpful to guide hemodynamic therapy.

OBJECTIVES: Sepsis associated encephalopathy (SAE) is a common neurological complication of sepsis. Delirium is a common symtom of SAE. The pathophysiology of SAE is still unclear, but several likely mechanisms have been proposed, such as mitochondrial and endothelial dysfunction, neurotransmission disturbances, derangements of calcium homeostasis, cerebral microcirculation dysfunction, and brain hypoperfusion. Near-infrared spectroscopy (NIRS) is a non-invasive measure for regional cerebral oxygen saturation (rSO METHODS: A total of 48 septic patients who admitted to the intensive care unit (ICU) of Xiangya Hospital, Central South University from August 2017 to May 2018, were retrospectively study. Septic shock was diagnosed according to the criteria of sepsis 3.0 defined by the American Association of Critical Care Medicine and the European Society of Critical Care Medicine. NIRS monitoring was performed during the first 6 hours admitted to ICU with sensors placed on the bilateral forehead of patients. The maximum (rSO RESULTS: The overall 28-day mortality of septic shock patients was 47.92% (23/48), and the incidence of delirium was 18.75% (9/48). The rSO CONCLUSIONS Cerebral anoxia and hyperoxia, as well as the large fluctuation of cerebral oxygen saturation are important factors that affect the outcomes and the incidence of delirium in septic shock patients, which should be paid attention to in clinical practice. Dynamic monitoring of cerebral oxygen saturation and maintain its stability may be of great significance in patients with septic shock.
APACHE ; Humans ; Intensive Care Units ; Oxygen Saturation ; Prognosis ; Retrospective Studies ; Sepsis ; Shock, Septic

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.

Since the cluster of the 2019 novel coronavirus (2019-nCoV) pneumonia, a large number of patients gathered, the mortality of critical patients has remained high and the treatment was unclear. In this outbreak, Hunan Changde region immediately set up a hospital and intensive care unit. The patients relieved through respiratory support, hemodynamics management, nutritional support, the application of antiviral drugs, analgesic and sedation. The treatment experience in severe cases of 2019-nCov pneumonia patients were summarized as follows: in terms of respiratory support, we needed to pay attention to the advantages of high-flow nasal cannula oxygen therapy (HFNC) and the intervention of mechanical ventilation, pay attention to the ventilator parameters, and adopt prone position timely. In the aspects of fluid resuscitation and volume management, we should pay attention to the characteristics of severe patients' volume status, perform early evaluation, and clinicians should focused on hemodynamic management beside the bed. In the aspect of nutritional support and evaluation and maintenance of intestinal function, early enteral nutrition should be adopted in time. However, the trade-off between the risk of intestinal function and nutritional support in patients with mechanical ventilation and the antiviral benefits of Kaletra needed to be reevaluated, the optimized way of analgesia and sedation was adopted, at the same time, the usage and side effects of antiviral drugs should be paid attention to. We should grasp the opportunity of transportation for severe patients. It is suggested that some warning scores should be used to facilitate early recognition of patients with severe infection and then they should be earlier transferred to the designated hospital for intensive care.

By observing the expression of peripheral blood lymphocyte programmed death-1 (PD-1) in patients with aneurysm subarachnoid hemorrhage (aSAH), the expression characteristics and significance in patients with aSAH were explored. Methods A total of 21 patients with aSAH were selected and were divided into neurological symptoms group [ Glaskow Coma Scale ( GCS) <15, 10 cases] and non-neurological symptoms group (GCS=15, 11 cases) according to GCS. And 6 health human were selected as the control group. The expression of CD4 + and CD8 + T lymphocytes in peripheral blood of patients in each group was detected by flow cytometry, and its characteristics and significance were analyzed. Results The percentages of PD-1 + CD4 + T lymphocyte and PD-1 +CD8 + T lymphocytein of non-neurological symptoms group were significantly higher than those in control group, while significantly lower than those in neurological symptoms group ( all P< 0.05 ). The percentages of PD-1 +CD4 + T lymphocyte and PD-1 +CD8 + T lymphocytein were significantly correlated with the GCS score, and the Spearson coefficients were 0.87 and 0.83, respectively (all P<0.05). In the aSAH patients, the incidence of pulmonary infection in neurological symptoms group was significantly higher than that in non-neurological symptoms group (P<0.05), and the percentages of PD-1 +CD4 + T lymphocyte and PD-1 +CD8 + T lymphocytein in pulmonary infection group was significantly higher than that in non-pulmonary infection group ( all P< 0.05 ). Conclusion In patients with aSAH, especially those with neurological symptoms, the expression intensity of CD4 +and CD8 + T lymphocyte PD-1 is significantly increased, which is correlated with the severity of neurological symptoms after aSAH and pulmonary infection after hemorrhage.

Objective: To investigate the clinical significance of transcranial Doppler (TCD) in early diagnosis of sepsis-associated encephalopathy(SAE). Methods: Septic patients admitted to the intensive care unit(ICU) were recruited at Xiangya Hospital, Central South University from July 2015 to March 2016. Clinical data and TCD parameters during 24 hours after admission were collected. All patients were screened for delirium using the confusion assessment method for the intensive care unit (CAM-ICU) twice a day. The gold standard of the diagnosis of SAE was positive CAM-ICU evaluation. Patients were divided into SAE group and the non-SAE group. TCD data including systolic velocity (Vs), diastolic velocity (Vd), mean velocity (Vm), pulsatility index (PI) and resistant index (RI) were analyzed to determine the optimal diagnostic cut-off value. Results: A total of 43 patients were enrolled including 12 in SAE group and 31 in non-SAE group. Vm and Vd were lower in SAE group [Vm: (53.50±12.22) cm/s vs. (61.68±9.63) cm/s, P<0.05; Vd: (33.42±10.87) cm/s vs. (43.16±7.84) cm/s, P<0.01] but PI and RI were significant higher in SAE group[PI:(1.16±0.2) vs. (0.90±0.15), P<0.01;RI:(0.65±0.08) vs. (0.56±0.06), P<0.01] than in non-SAE group. The cut-off values of Vs, Vm, Vd, PI and RI for the diagnosis of SAE were 112cm/s, 55.50cm/s, 34.50cm/s, 1.16, 0.65, respectively, with the relevant sensitivities of 19.4%, 83.9%, 93.5%, 58.3%, 58.3% and the specificities of 100.0%, 50.0%, 58.3%, 96.8%, 96.8%, respectively. The diagnostic AUC of Vd, PI and RI were 0.741, 0.808 and 0.808 respectively. Conclusions The parameter changes of TCD suggest that the pathogenesis of SAE is related to cerebral hypoperfusion, TCD is a helpful method for the early diagnosis of SAE.

Objective To evaluate the role of combining relative alpha variability and electroencephalogram (EEG) reactivity to predict the prognosis of hypoxic?ischemic encephalopathy(HIE) in adult patients. Methods A total of 28 adult patients with HIE admitted to general intensive care unit at Xiangya Hospital in Central South University were enrolled in this observational study from January2016 to April 2017. These patients with body temperature over 35℃after 72?hour admission could be continuously monitored at least 12 hours byEEG.At the same time,each patient was assessed for EEG reactivity.Then we analyzed the correlation between EEG reactivity, relative alpha variability and clinical prognosis. Results EEG reactivity was elicited in 15/28 patients, among whom 12 patients had a good outcome. While in the other 13 patients, EEG reactivity was not elicited, among whom only 3 patients had a good outcome. As to the results ofrelative alpha variability,11/13 patients with degree 3?4were of good prognosis; while only 3/15 patients with degree 1?2 were of good prognosis. Glasgow coma scale(GCS), EEG reactivity, and relative alpha variability were correlated with clinical outcome(χ2=5.073,9.073,-3.626, respectively,all P<0.05). The sensitivity of GCS, EEG reactivity,and relative alpha variability to predict the poor prognosis were 69.2%, 76.9%, 84.6%, respectively. The specificity were 73.3%, 80.0%, 73.3%, respectively. The consistency rates were 71.4%, 78.6%, 78.6%, respectively. The positive predictive values were 69.2%, 76.9%, 73.3%, respectively. The negative predictive values were 73.3%, 80.0%, 84.6%, respectively. More importantly, the accuracy of the relative alpha variability combined with EEG reactivity for the prediction of poor prognosis was much higher with the positive predictive value of 90.0%,the specificity of 93.3%,the sensitivity of 69.2%, the consistency rate of 82.1%,and the negative predictive values of 77.8%. Conclusions The combination of relative alpha variability and EEG reactivityis reliable to predict clinical outcome of patients with HIE.