1.Application of Micro-Magnetic Resonance Imaging in the Study with Animal in Vivo Models of Neurological and Psycholic Disorders
International Journal of Cerebrovascular Diseases 2008;16(8):631-634
The complexity of human organism determines a great deal of research work should be realized by dynamic research in animal models in vivo.The development of micro-magnetic resonance imaging technique and its application in animal model of neurological and psychotic disorders have opened up a new way for promoting the study of neurological and psychotio disorders in depth and development from the information about neurological anatomy in vivo to the measurement of specific molecular target.
2.The predictive value of dynamic arterial elastance in arterial pressure response after norepinephrine dosage reduction in patients with septic shock
Fengming LIANG ; Ting YANG ; Liang DONG ; Jiaojie HUI ; Jie YAN
Chinese Journal of Internal Medicine 2017;56(5):344-348
Objective To assess whether dynamic arterial elastance (Eadyn)can be used to predict the reduction of arterial pressure after decreasing norepinephrine (NE) dosage in patients with septic shock.Methods A prospective observational cohort study was conducted.Thirty-two patients with septic shock and mechanical ventilationwere enrolledfrom January 2014 to December 2015 in ICU of Wuxi People's Hospital of Nanjing Medical University.Hemodynamic parameters were recorded by pulse contour cardiac output(PiCCO) monitoring technology before and after decreasing norepinephrine dosage.Eadyn was defined as the ratio of pulse pressure variation (PPV) to stroke volume variation (SVV).Mean arterial pressure (MAP) variation was calculated after decreasing the dose of NE.Response was defined as a ≥ 15%decrease of MAP.AUC was plotted to assess the value of Eadyn in predicting MAP response.Results A total of 32 patients were enrolled in our study,with 13 responding to NE dose decrease where as the other 19 did not.Eadyn was lower in responders than in nonresponders (0.77 ± 0.13 vs 1.09 ± 0.31,P < 0.05).Baseline Eadyn was positively correlated with systolic blood pressure variation,diastolic blood pressure variation,systemic vascular resistance variation and MAP variation (r =0.621,P =0.000;r =0.735,P =0.000;r =0.756,P =0.000;r =0.568,P =0.000 respectively).However,stoke volume variation,baseline level of systemic vascular resistance and NE baseline dose were not correlated with Eadyn baseline value (r =0.264,P =0.076;r =0.078,P =0.545;r =0.002,P =0.987 respectively).Eadyn ≤ 0.97 predicted a decrease of MAP when decreasing NE dose,with an area under the receiver-operating characteristic curve of 0.85.The sensitivity was 100.0% and specificity was 73.7%.Conclusions In septic shock patients treated with NE,Eadyn is an index to predict the decrease of arterial pressure in response to NE dose reduction.
3.Enriched environment and antidepressant treatment during juvenility overcome the memory deficits and depressive-like behavior induced by early adverse stress
Shanshan LIU ; Zhijun ZHANG ; Jiaojie HUI ; Guangjun XI ; Daihua LIN ; Xiangrong ZHANG
Chinese Journal of Behavioral Medicine and Brain Science 2010;19(5):385-388
Objective To explore the effect of postweaning enriched environment and citalopram treatment during juvenility on the behaviour of male rats exposed to early adverse stress. Methods The newborn pups were randomly divided into maternal separation group (MS) and non-maternal separation group (NMS). Offspring were weaned on PND22 and housed in same-rearing groups under either standard or enriched conditions or citalopram treatment until adulthood. All of them were examined by sucrose consumption test, forced swimming test (FST) and morris water maze test (MWZ). Results (1) MS had significantly less consumption of sucrose intake (ml/g)(0.013 ±0.006, n = 10), compared with the following five groups (MS + EE (0.023 ±0.012, n = 8); MS + Drug (0.027 ±0.012, n = 9); NMS (0.022 ± 0. 007, n=11);NMS + EE (0.023 ±0.007, n = 7); NMS + Drug (0.032 ±0.011),n=7)), NMS + Drug had significantly increased the radio of sucrose consumption on NMS group. (2)The immobility in FST were longer in MS-experienced groups (MS (140. 19 ± 37.01) s, n = 8); MS + EE (129.41 ±29.50)s, n = 6) ;NMS + Drug (128.83 ±26. 11)s, n = 6)) than three non-MS groups (NMS (96.28 ±35.63)s,n = 7); NMS + EE (94.17 ±24. 87)s, n = 6) ;NMS + Drug (93.00 ±34. 21)s, n = 6)). (3) MS had shorter time and shorter percentage of distance spent in target quadrant in MWZ,citalopram treatment markedly improved spatial memory on NMS group. Conclusion Maternal separation applied in newborn rats induces a broad spectrum of behavioral changes reminiscent of depressive symptoms in humans, which might be reversed to some extent by EE and antidepressant in young adults.
4.Under-expression of LATS1 promotes the differentiation, proliferation and migration of mesenchymal stem cells by inhibition the Hippo signaling pathwayin vitro
Lang LI ; Liang DONG ; Jiaojie HUI ; Fei GAO ; Qiuhui WANG ; Lan YANG ; Jiangqian ZHANG ; Jie YAN
Chinese Critical Care Medicine 2017;29(8):731-737
Objective To explore the effects of under-expression of large tumor suppressor 1 (LATS1) on activation of Hippo signaling pathway and differentiation, proliferation, migration of bone marrow mesenchymal stem cells (mMSCs) of micein vitro.Methods mMSCs of C57BL/6 mice were divided into normal control (MSC) group, empty vector control (MSC-GFP) group, LATS1-over-expressing (MSC-LATS1) group, empty vector without LATS1 shRNA control (MSC-shControl) group and LATS1-under-expressing (MSC-shLATS1) group. Lentiviral vectors with activated,inactivated LATS1 (the key molecule of Hippo signaling pathway) modifications and empty vectors were constructed and were used to infect mMSCsin vitro. The transduction efficiencies mediated by the lentiviral vectors were evaluated by fluorescence microscopy and flow cytometry. The mRNA expression of LATS1 was quantified by quantitative real-time polymerase chain reaction (qRT-PCR), and the protein expressions of LATS1, YAP (p-YAP), 14-3-3 were quantified by Western Blot to evaluate the activation of Hippo signaling pathway. Osteogenic and adipogenic differentiation of mMSCs were evaluated through measurement of Runx2, OSX and C/EBPα, PPAR-γ mRNA by qRT-PCR, as well as Alizarin Red S and Oil red O staining. Proliferation of mMSCs was evaluated using methy thiazdyl tetrazolium (MTT) assay. The scratch test and Transwell chamber test were used to analyze the horizontal and vertical migration ability of mMSCs.Results The transduction efficiencies mediated by the lentiviral vectors were 94.74%-96.10%. Compared with MSC-GFP group, the activation of Hippo signaling pathway was promoted in MSC-LATS1 group [LATS1 mRNA (2-ΔΔCT): 4.37±0.21 vs. 1.20±0.04, LATS1 protein (gray value): 2.21±0.06 vs. 1.09±0.10, p-YAP/YAP protein (gray value): 1.51±0.13 vs. 0.98±0.05, 14-3-3 protein (gray value): 1.92±0.18 vs. 1.10±0.09, allP < 0.05], osteogenic and adipogenic differentiation of mMSCs were decreased in MSC-LATS1 group [mineralization (A value):0.13±0.02 vs. 0.40±0.03, Runx2 mRNA (2-ΔΔCT): 0.51±0.02 vs. 0.98±0.09, OSX mRNA (2-ΔΔCT): 0.41±0.04 vs. 1.04±0.09, lipid accumulation (A value): 0.10±0.02 vs. 0.25±0.03, C/EBPα mRNA (2-ΔΔCT): 0.33±0.03 vs. 1.11±0.09, PPAR-γ mRNA (2-ΔΔCT): 0.29±0.02 vs. 1.04±0.10, allP < 0.05], the proliferation rate of mMSCs at 4-7 days was decreased in MSC-LATS1 group and so were the horizontal and vertical migration of mMSCs [wound healing rate: (18.65±3.53)% vs. (40.29±1.87)%, migrated cells (cells/MP): 35.99±6.18 vs. 103.67±17.77, bothP <0.05]. Compared with MSC-shControl group, the activation of Hippo signaling pathway was inhibited in MSC-shLATS1 group [LATS1 mRNA (2-ΔΔCT): 0.16±0.01 vs. 0.98±0.03, LATS1 protein (gray value): 0.38±0.03 vs. 1.04±0.07, p-YAP/YAP protein (gray value): 0.58±0.04 vs. 1.05±0.06, 14-3-3 protein (gray value): 0.14±0.02 vs. 1.02±0.09, allP < 0.05], osteogenic and adipogenic differentiation of mMSCs were increased in MSC-shLATS1 group [mineralization (A value): 0.93±0.13 vs. 0.44±0.05, Runx2 mRNA (2-ΔΔCT): 1.44±0.12 vs. 0.95±0.04, OSX mRNA (2-ΔΔCT):1.67±0.06 vs. 1.10±0.11, lipid accumulation (A value): 0.47±0.06 vs. 0.28±0.04, C/EBPα mRNA (2-ΔΔCT):3.98±0.61 vs. 0.99±0.10, PPAR-γ mRNA (2-ΔΔCT): 3.05±0.36 vs. 0.98±0.14, allP < 0.05], the proliferation rate of mMSCs at 3-7 days was increased in MSC-shLATS1 group and so were the horizontal and vertical migration of mMSCs [wound healing rate: (80.18±6.98)% vs. (46.18±1.01)%, migrated cells (cells/MP): 212.69±41.21 vs. 115.87±35.15, bothP < 0.05].Conclusions Under-expression of LATS1 promotes the differentiation, proliferation, migration of mMSCs by inhibition of Hippo signaling pathwayin vitro.
5.Effects of Hippo pathway on differentiation, proliferation, migration of bone marrow mesenchymal stem cells in vitro
Lang LI ; Liang DONG ; Yizhe CHEN ; Jiaojie HUI
Chinese Critical Care Medicine 2019;31(6):750-755
Objective To explore the effects of Hippo pathway on differentiation, proliferation, and migration of bone marrow mesenchymal stem cells (BMSCs) in vitro. Methods BMSCs of C57BL/6 mice were identified using fluorescence-activated cellsorting analysis and the capabilities of osteogenic, chondrogenic and adipogenic differentiation were evaluated. The differentiation of BMSCs to typeⅡalveolar epithelial cells (AECⅡ) was induced by indirect co-culture with mouse lung epithelial cells (MLE-12) and small airway epithelial cell growth medium (SAGM). The Hippo pathway was regulated by 2-deoxy-D-glucose (2-DG) and 9E1, the effects of 2-DG and 9E1 on the expression of BMSCs surface proteins (SPB, SPC and SPD) mRNA and pro-SPC protein were detected by real time quantitative polymerase chain reaction (qRT-PCR) and Western Blot. The effect of Hippo pathway on differentiation of BMSCs to AECⅡ cells was evaluated. The effect of Hippo pathway on the proliferation of BMSCs was evaluated by methyl thiazolyl tetrazolium (MTT) assay (intervention of 0.1, 0.5, 1.0, 5.0 mmol/L 2-DG). The scratch test and Transwell chamber test were used to analyze the effect of Hippo pathway on migration ability of BMSCs to conditioned medium of acute respiratory distress syndrome (ARDS) lung tissue. Results 2-DG could activate Hippo pathway in a dose-dependent manner and promote the differentiation to AECⅡ and proliferation of BMSCs, the maximum effects were observed after 5 mmol/L of 2-DG treatment [SPB mRNA (2-ΔΔCT): 2.42±0.28 vs. 1.89±0.11, SPC mRNA (2-ΔΔCT): 8.06±0.68 vs. 6.59±0.79, SPD mRNA (2-ΔΔCT): 6.45±0.37 vs. 5.27±0.28, pro-SPC/β-actin: 5.80±1.86 vs. 4.93±1.18, proliferation rate:(145.46±18.18)% vs. (98.91±4.36)%, all P < 0.05], but 9E1 could reverse those effects through inhibition of Hippo pathway [SPB mRNA (2-ΔΔCT): 1.32±0.17 vs. 1.89±0.11, SPC mRNA (2-ΔΔCT): 3.91±0.34 vs. 6.59±0.79, SPD mRNA (2-ΔΔCT): 3.38±0.25 vs. 5.27±0.28, pro-SPC/β-actin: 2.48±0.17 vs. 4.93±1.18, proliferation rate: (80.00±7.27)% vs. (98.91±4.36)%, all P < 0.05]. The ability of horizontal migration [wound healing: (27.17±3.53)% vs. (52.45±6.52)%, P < 0.05] and homing BMSCs to conditioned medium of ARDS lung tissue [cell count (fold, relative to control): 2.77±0.21 vs. 1.90±0.19, P < 0.05] were increased after activation of Hippo pathway by 2-DG treatment, but those effects were reversed after inhibition of Hippo pathway by 9E1 treatment [wound healing: (79.89±8.42)% vs. (52.45±6.52)%, cell count (fold, relative to control): 1.69±0.13 vs. 1.90±0.19, both P < 0.05]. Conclusion Activation of Hippo pathway could enhance differentiation of BMSCs to AECⅡ, promote proliferation and ability of horizontal migration and homing BMSCs to conditioned medium of ARDS lung tissue in vitro.
6.Influence of transcutaneous oximetry on septic shock-associated acute kidney injury
Liang DONG ; Xiuhong ZHANG ; Fengming LIANG ; Jiaojie HUI ; Jie YAN ; Zheng YAN ; Lang LI
Chinese Journal of Emergency Medicine 2017;26(9):999-1004
Objective To explore the influence of transcutaneous oximetry on septic shock-associated acute kidney injury (AKI) in intensive care unit (ICU).Methods Forty-nine patients with septic shock admitted in the ICU of Wuxi People's Hospital Affiliated to Nanjing Medical University were enrolled from January 2013 to December 2015.The 10 min oxygen challenge test was conducted using transcutaneous oximetry just before (0 h) and 6 h after initiation of fluid resuscitation,and 10 min oxygen challenge test data (10 min OCT) at 0 h and 6 h were then calculated,respectively.The enrolled patients were divided into low 10 min OCT group (10 min OCT < 66 mmHg,L group) or high 10 min OCT group (10 min OCT ≥66 mmHg,H group) according to the 10 min OCT value at 6 h.The hemodynamic variables [mean arterial pressure (MAP),central venous pressure (CVP)],oxygen metabolism indexes [central venous oxygen saturation (ScvO2),arterial lactate (Lac)],dose of vasoactive agents,10 min OCT at 0 h and 6 h were recorded.APACHE Ⅱ score,incidence and severity of septic shock-associated AKI,frequency of CRRT,ICU mortality and 28 d mortality were compared between groups using SPSS 22.0 software,risk factors associated with prognosis were analyzed using COX regression model.Results There were 27 cases in L group and 22 cases in H group.The MAP,CVP,ScvO2,lactate level and dose of vasoactive agents were comparable between groups at 0 h or 6 h (P > 0.05),while 10 min OCT at 6 h was higher in H group than that inLgroup [(77.6±18.5) mmHgvs.(51.3 ±21.6) mmHg,P<0.05].The incidence of septic shock-associated AKI (77.8% vs.50.0%,P < 0.05),proportion of phase 3 AKI (44.4%vs.22.7%,P <0.05) and frequency of CRRT (48.1% vs.22.7%,P <0.05) was higher in L group than those in H group,and similarly were the ICU mortality (51.8% vs.22.7%,P <0.05) and 28 d mortality (63.0% vs.31.8%,P < 0.05).Therefore,the 6 h 10 min OCT ≥66 mmHg was a protective factor to improve the ICU mortality (RR =0.01,95% CI:0.001-0.39,P < 0.05) and 28 d mortality (RR =0.01,95%CI:0.001-0.27,P<0.05) in patients with septic shock-associated AKI.Conclusions 10 min OCT imposes substantial influence on the incidence,severity and prognosis of patients with septic shockassociated AKI,oxygen challenge test could improve the treatment of septic shock-associated AKI.
7.Modulation of Hippo signaling pathway facilitates mesenchymal stem cells to repair lung injury in murine lipopolysaccharide induced acute respiratory distress syndrome
Liang DONG ; Lang LI ; Yizhe CHEN ; Jiaojie HUI
Chinese Journal of Emergency Medicine 2019;28(7):855-862
Objectives To determine the effect of Hippo signaling pathway on lung injury repair of bone-marrow derived mesenchymal stem cells (mMSCs) in murine lipopolysaccharide (LPS) induced acute respiratory distress syndrome (ARDS).Methods C57BL/6 mouse bone marrow-derived MSC (mMSCs) cell lines with low expression of large tumor suppressor 1 (LATS 1) were constructed by lentiviral vector transfection.ARDS was modeled by intratracheally injection of 2 mg/mL lipopolysaccharide (LPS)50 μL.C57BL/6 mice were randomly(random number) divided into four groups (n=36):normal control group,ARDS group,ARDS mice transplanted with mMSCs transfected with blank lentivirus vector (MSC-shcontrol group) or sh-LATS 1 lentivirus vector (MSC-shLATS 1 group).Mice were sacrificed at 3,7,and 14 d after modeling,and lung tissue and bronchoalveolar lavage fluid (BALF) were collected.Near-infrared fluorescence imaging,immunofluorescence staining and Western blot were used to evaluate retention and differentiation of mMSCs in lung tissue.Lung tissue wet weight/body weight ratio (LWW/BW) and total protein (TP) and albumin (ALB) in BALF were determined to reflect pulmonary edema.The expression of Occludin protein in lung epithelium was tested by Western blot.The levels of interleukins (IL-1β,IL-6,and IL-10) in BALF were assessed by enzyme-linked immunosorbent assay (ELISA).Lung injury score and pulmonary fibrosis score in lung tissue were assessed.Results The retention ofmMSCs at 3,7 and 14 d in the MSC-shLATS1 group were significantly higher than those in the MSC-shcontrol group [(26.25±4.58) vs (12.13±3.75) cells/HP,(20.49±3.86) vs (9.97±2.76) cells/HP,and (13.77±3.55) vs (6.89±2.10) cells/HP.all P<0.05],so was the differentiation of mMSCs into type Ⅱ alveolar epithelial cells at 14 d [(64.12±15.29)% vs (19.64±3.71)%,P<0.05].LWW/BW and TP and ALB in BALF at 3 and 14 d in the MSC-shLATS1 group [(9.85±1.51),(6.11±0.83) (mg/g) and (5.12±0.87),(3.05±0.87) (mg/mL)and (0.44±0.18),(0.33±0.04) (mg/mL)] were higher than those in the MSC-shcontrol group [(14.88± 1.74),(8.04±l.70)(mg/g) and (8.08±1.72),(5.94±1.20) (mg/mL) and (0.71±0.21),(1.07±0.29) (mg/mL)] (all P<0.05),so was the relative expression of Occludin protein[(0.79±0.11) vs (0.49±0).19),(P<0.05)].The levels of IL-1β and IL-6(pg/mL) in BALF in the MSC-shLATS1 group [(60.11±8.58),(101.74±11.55)] was lower than those in the MSC-shcontrol group [(99.26±14.32),(145.54±13.29)] (all P<0.05),but the levels of IL-10 in BALF in the MSC-shLATS 1 group (316.65±37.88)pg/mL was higher than those in the MSC-shcontrol group (190.83±22.61)pg/mL (P<0.05).Lung injury scores at 3 and 14 d in the MSC-shLATS1 group [(7.18±1.12),(3.33±0.49)] was lower than those in the MSC-shcontrol group [(9.72±1.45),(5.11±0.86)] (all P<0.05),so was pulmonary fibrosis score at 14 d [(0.68±0.12) vs (1.47±0.18),P<0.05].Conclusion Inhibition of Hippo signaling pathway through underexpression of LATS1 could improve the therapeutic effects of mMSCs in murine LPS-induced ARDS.
8.Effects of Hippo signaling on anti-oxidative stress of mesenchymal stem cells in vitro
Lang LI ; Liang DONG ; Jiaojie HUI ; Fei GAO ; Qiuhui WANG ; Lan YANG ; Jiangqian ZHANG ; Jie YAN
Chinese Critical Care Medicine 2018;30(4):296-301
Objective To explore the effects of Hippo signaling on anti-oxidative stress of mouse marrow mesenchymal stem cells (mMSCs) in vitro. Methods mMSCs derived from C57BL/6 mice were identified using fluorescence-activated cell sorting analysis and the capabilities of osteogenic, chondrogenic and adipogenic differentiation were evaluated. 2-deoxy-D-glucose (2-DG) or XMU-MP-1 was used to modulate Hippo signaling. Oxidative stress was induced by H2O2treatment and the effect of oxidative stress induced by H2O2on survival of mMSCs was evaluated using methyl thiazolyl tetrazolium (MTT) assay. The effect of oxidative stress induced by H2O2on Hippo signaling and the effect of Hippo signaling on capability of anti-oxidative stress of mMSCs were analyzed through apoptosis-regulated proteins (Bcl-2 and Bax) using Western Blot. Results Hippo signaling was activated by 2-DG in a concentration-dependent manner and the effect was most prominent by 5 mmol/L of 2-DG [compared with the blank control group, large tumor suppressor 1 (LATS1) protein (grey value): 2.33±0.25 vs. 0.98±0.03, phosphorylated Yes-associated protein (p-YAP)/YAP protein ratio (grey value): 2.30±0.35 vs. 1.01±0.05, 14-3-3 protein (grey value):2.19±0.40 vs. 0.99±0.04, all P < 0.05]; Hippo signaling was inhibited by 100 nmol/L of XMU-MP-1 [compared with the blank control group, LATS1 protein (grey value): 0.69±0.10 vs. 0.98±0.03, p-YAP/YAP protein ratio (grey value):0.65±0.06 vs. 1.01±0.05, 14-3-3 protein (grey value): 0.75±0.11 vs. 0.99±0.04, all P < 0.05]. Death of mMSCs was induced by H2O2in a concentration-dependent manner and the minimal effective concentration was 0.1 mmol/L [compared with the blank control group, survival rate of mMSCs: (81.25±11.85)% vs. (100.44±12.39)%, P < 0.05]. Inhibition of Hippo signaling was induced by H2O2in a concentration-dependent manner and the minimal effective concentration was also 0.1 mmol/L [compared with the blank control group, LATS1 protein (grey value): 0.75±0.06 vs. 1.01±0.09, p-YAP/YAP protein ratio (grey value): 0.69±0.05 vs. 0.98±0.05, both P < 0.05], those effects might associate with reduction of Bcl-2/Bax ratio (grey value: 0.48±0.18 vs. 1.06±0.09, P < 0.05). Compared with the treatment of 0.1 mmol/L of H2O2, activation of Hippo signaling by 5 mmol/L of 2-DG [ LATS1 protein (grey value):0.95±0.05 vs. 0.64±0.06, p-YAP/YAP protein ratio (grey value): 0.87±0.03 vs. 0.45±0.16, both P < 0.05] improved survival of mMSCs [(92.80±9.43)% vs. (75.47±9.43)%, P < 0.05] through an increase of Bcl-2/Bax ratio (grey value:1.14±0.16 vs. 0.77±0.12, P < 0.05); however, inhibition of Hippo signaling by 100 nmol/L of XMU-MP-1 [ LATS1 protein (grey value): 0.39±0.03 vs. 0.64±0.06, p-YAP/YAP protein ratio (grey value): 0.28±0.04 vs. 0.45±0.16, both P < 0.05] decreased survival of mMSCs [(57.54±4.59)% vs. (75.47±9.43)%, P < 0.05] through an decrease of Bcl-2/Bax ratio (grey value: 0.63±0.20 vs. 0.77±0.12, P < 0.05). Compared with normal lung tissue, acute respiratory distress syndrome (ARDS) lung tissue markedly activate Hippo signaling in mMSCs [LATS1 protein (grey value): 1.71± 0.08 vs. 1.00±0.10, p-YAP/YAP protein ratio (grey value): 2.46±0.39 vs. 1.01±0.04, 14-3-3 protein (grey value):2.27±0.52 vs. 1.01±0.08, all P < 0.05]. Conclusion Hippo signaling could affect survival and capability of anti-oxidative stress of mMSCs via modulation of Bcl-2/Bax ratio in vitro.
9.Dynamic association of plasma brain-derived neurotrophic factor, neuron-specific enolase, and S100βwith delirium in critically ill patients
Jiaojie HUI ; Zheng YAN ; Fengming LIANG ; Liang DONG ; Zhidong ZANG ; Qiuhui WANG ; Jie YAN
Chinese Journal of Emergency Medicine 2018;27(10):1132-1135
Objective To determine the association between plasma concentrations of brain derived neurotrophic factor (BDNF), neuron-specific enolase (NSE), and S100β, and the occurrence of delirium in critically ill patients. Methods Totally 65 patients in Intensive Care Unit (ICU) of Wuxi People's Hospital of Nanjing Medical University between June 2015 and February 2016 were included in the present study. Delirium diagnosis was used by confusion assessment method for the ICU (CAM-ICU). Plasma BDNF, NSE, and S100β concentrations were determined on day 1(T1), 3(T3), and 10(T10) after ICU admission. The day of ICU admission was defined as T0. Results Compared with the plasma BDNF level on T1 (0.23±0.22) μg/L, the plasma BDNF level on T3 (0.59±0.34) μg/L and T10 (0.24±0.21) μg/L were higher, especially for that on T3 with a significant difference (F=21.58, P=0.018). Plasma NSE level on T3 (1.68±0.25) μg/L was significantly higher than that on T1 (1.22±0.32) μg/L (F=10.24, P=0.042). Compared with those without delirium, the delirious patients had lower BDNF, higher NSE and S100β on T1, T3 and T10, of which the difference of BDNF [T1: (0.23±0.22) μg/L vs. (1.02±0.24) μg/L, F=116.25,P<0.01; T3: (0.59±0.34) μg/L vs. (1.55±0.36) μg/L, F=82.39, P<0.01; T10: (0.24±0.21) μg/L vs. (1.09±0.55)μg/L, F=50.93, P=0.003, and NSE (T1: (1.22±0.32) μg/L vs. (0.47±0.23) μg/L, F=94.30, P<0.01;T3:(1.68±0.25) μg/L vs. (0.79±0.28) μg/L, F=78.63, P=0.017; T10: (0.98±0.37) μg/L vs. (0.51±0.22) μg/L, F=70.95, P=0.026) reached significant differences. Conclusions Plasma BDNF and NSE are closely related to the occurrence of delirium in critically ill patients, especially for BDNF. Clinical monitoring of plasma levels of BDNF can help to predict the outcome of brain function in critically ill patients.
10.Clinical study on neutrophil to lymphocyte ratio and neutrophil extracellular traps with liver injury in patients with sepsis
Fei GAO ; Song GAO ; Jiaojie HUI ; Fengming LIANG ; Ting YANG
Chinese Journal of Emergency Medicine 2021;30(12):1484-1488
Objective:To explore the clinical value of peripheral blood neutrophil-to-lymphocyte ratio (NLR) combined with neutrophil extracellular traps (NETs) in predicting liver injury in patients with sepsis.Methods:A prospective observational study was conducted. The patients who met the diagnostic criteria for sepsis 3.0 admitted to the Department of Intensive Care Unit in Wuxi People’s Hospital Affiliated to Nanjing Medical University from March 2019 to June 2020 were selected as the research objects. The basic informations of the patients were recorded. NLR based on blood routine at admission was calculated. PicoGreen fluorescence quantitative detection kit was used to detect the quantitative level of free DNA (cf-DNA/NETs) in the peripheral plasma of patients at admission. According to whether liver injury occurred, the patients were divided into the sepsis without liver injury group and sepsis with liver injury group. Binary Logistics regression analysis was used to predict the risk factors of sepsis with liver injury. The receiver operating characteristic (ROC) curve was drawn. The value of NLR, NETs, NLR combined with NETs in predicting liver injury in patients with sepsis was analyzed.Results:A total of 122 patients with sepsis were enrolled, of which 45 patients suffered from septic liver injury, with an incidence rate of 36.89%. The NLR of the sepsis wth liver injury group was (21.63 ± 4.71), the NLR of the sepsis without injury injury group was (15.03 ± 4.71), and the NETs level of the sepsis with liver injury group was (505.86 ± 250.05) μg/L, the level of NETs in the sepsis without liver injury group was (179.27 ± 67.20) μg/L, and the differences between the two groups were statistically significant (all P<0.05). Binary logistic regression analysis found that NLR ( OR=1.470, 95% CI: 1.121-1.926, P<0.05) and NETs ( OR=1.018, 95% CI: 1.005-1.030, P<0.05) at admission were the independent risk factors for liver injury in patients with sepsis. The best cut-off value of NLR was 16.68, and the best cut-off value of NETs was 317 μg/L. The sensitivity of combined application of NLR and NETs to predict liver injury in patients with sepsis was 77.78%, specificity was 98.70%, the area under the curve was 0.930, and the Youden Index was 0.765. Conclusions:The peripheral blood NLR and NETs levels are independent risk factors for liver injury in patients with sepsis. The combined application of NLR and NETs has a certain predictive value for liver injury in patients with sepsis. Taking NLR of 16.68 and NETs of 317 μg/L as the cut-off values, they can be used as early warning indicators to predict liver injury in patients with sepsis.