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Objective To investigate whether Andrographolide(AG)can alleviate intestinal injury in sepsis by ac-tivating the SLC7A11/GPX4 axis in ferroptosis.Methods Forty rats were randomly divided into sham group(sham group),sepsis group(CLP group),AG low,medium and high dose groups(5,10 and 20 mg/kg).HE staining was used to observe the pathological changes of Intestinal tract.ELISA method was used to determine Inter-leukin 6(IL-6),tumour necrosis factor α(TNF-α),intestinal fatty acid binding protein(I-FABP),D-lactate content.The mechanism of ferroptosis was explored with AG high dose group(AG20 group),forty rats were ran-domly divided into sham group,CLP group,ferroptosis inhibitor(Fer-1)group,AG20+Fer-1 group.HE staining and transmission electron microscopy were used to observe the pathological changes of Intestinal tract.The kits were used to determine oxidative stress MDA,GSH levels and Fe3+content.Western blot was used to detect the protein levels of solute carrier family 7 member 11(SLC7A11),glutathione peroxidase 4(GPX4),and ferritin heavy poly-peptide 1(FTH-1).Results Compared with the sham group,the CLP group showed severe morphological damage to the small intestine,with significantly higher levels of inflammation,I-FABP and D-lactate(all P＜0.05),the AG group reversed these changes in a concentration-dependent manner(all P＜0.05).Compared with the CLP group,the AG20 and Fer-1 groups showed improved pathological damage to the small intestine,with lower levels of MDA and Fe3+and higher levels of GSH,SLC7A11,GPX4 and FTH-1 protein expression increased(all P＜0.05),and pathological injury and oxidative stress were reduced in the AG20+Fer-1 group,and SLC7A11,GPX4 and FTH-1 protein expression increased more significantly(all P＜0.05).Conclusion The mechanism by which AG attenuates intestinal injury in sepsis may be related to SLC7A11/GPX4 axis activation in ferroptosis.
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Objective @#To investigate whether NaHS，a hydrogen sulfide donor，can improve myocardial injury in sepsis by inhibiting oxidative stress and activating the Xc －/ GPX4 signaling pathway in ferroptosis．@*Methods @#Lipopolysacc-haride(LPS) induced H9c2 in rat cardiomyocytes to form an in vitro model of myocardial injury in sep- sis，which was divided into Control group，LPS group and LPS + NaHS group．The kits were applied to detect the changes of cardiomyocyte viability，Fe2 + ，LDH and CK-MB，determine the levels of oxidative stress indexes GSH and MDA，detect the changes of cellular ROS and mitochondrial membrane potential levels by fluorescent probes， and detect the expression levels of ferroptosis regulatory proteins SLC7A11 and GPX4 by Western blot. @*Results@#Compared with the Control group，H9c2 cell viability decreased，Fe2 + concentration increased ，GSH ，MDA and ROS levels increased，mitochondrial JC-1 monomer increased ，expression levels of ferroptosis regulatory proteins SLC7A11 and GPX4 decreased，and cell damage increased after LPS stimulation (P＜0. 05) ．Compared with the LPS group，NaHS attenuated LPS-induced H9c2 cell injury and elevated Fe2 + concentration，decreased the level of LPS-induced oxidative stress in H9c2 cells ，and increased the expression levels of ferroptosis regulatory proteins SLC7A11 and GPX4 (P＜0. 05 ) ．@*Conclusion @#The mechanism by which NaHS attenuates myocardial injury in sepsis may be related to the inhibition of oxidative stress and activation of the Xc －/ GPX4 signaling pathway in fer- roptosis.
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Objective:To observe the value of heart-type fatty acid-binding protein (H-FABP) and echocardiographic indexes in the diagnosis of cardiac insufficiency in sepsis.Methods:A prospective observational study was conducted. Eighty patients with sepsis admitted to the department of critical care medicine of the First Affiliated Hospital of Medical College of Shihezi University from October 2016 to January 2018 were enrolled. General clinical data such as gender, age, acute physiology and chronic health evaluationⅡ(APACHEⅡ), sequential organ failure assessment (SOFA) score, hospitalization time and 28-day mortality were recorded. Echocardiographic indexes at 1, 3, 7, 10 days after diagnosis, and white blood cell (WBC), neutrophilic granulocyte percentage (N%), N-terminal pro-brain natriuretic peptide (NT-proBNP), serum H-FABP level were recorded. Sepsis patients were divided into normal cardiac function group ( n = 30) and cardiac insufficiency group ( n = 50) according to cardiac function, the differences of echocardiographic indexes and cardiac markers between the two groups at different time points were compared. Logistic regression was used to screen out cardiac ultrasound indexes and cardiac markers that affect the occurrence of cardiac dysfunction in sepsis patients, and then receiver operating characteristic (ROC) curve analysis was performed. Results:Comparing the general data of the two groups, only the SOFA score of the cardiac insufficiency group was significantly higher than that of the normal cardiac function group (6.12±4.09 vs. 4.57±2.45, P < 0.05). N% and H-FABP in cardiac insufficiency group were higher than those in normal cardiac function group at the same time (N%: F = 6.973, P = 0.010; H-FABP: F = 17.303, P = 0.000). Without considering the time factor, there were significant differences in left ventricular end-diastolic volume (LVEDV), left ventricular end-systolic volume (LVESV), left ventricular ejection fraction (LVEF), stroke volume (SV), cardiac output (CO), left ventricular fractional shortening (LVFS), E-point of septal separation (EPSS), isovolumic relaxation time (IVRT), E peak deceleration time (EDT), A peak duration (Ad), left ventricular systolic pulmonary vein velocity (S), blood flow velocity of pulmonary vein in early left ventricular diastolic period (D), tricuspid orifice early diastolic blood flow velocity (E'), tricuspid orifice late diastolic blood flow velocity (A'), systolic velocities of the right ventricular free wall tricuspid annulus (Sm), and pulmonary valve annulus blood flow velocity (PVBV) between the two groups. ROC curve analysis of cardiac ultrasound indicators and cardiac markers screened by Logistic regression showed that the area under ROC curve (AUC) and the positive and negative predictive values were: LVEDV was 0.636, 77.30%, 56.03%; SV was 0.779, 88.82%, 71.19%; LVEF was 0.753, 92.12%, 55.21%; CO was 0.754, 88.82%, 77.19%; LVFS was 0.728, 81.25%, 66.99%; EPSS was 0.663, 96.99%, 51.56%; IVRT was 0.775, 86.97%, 73.55%; A' was 0.908, 96.58%, 89.60%; Sm was 0.738, 93.37%, 56.77%; H-FABP was 0.673, 80.26%, 57.25%, respectively. H-FABP was tested in parallel with LVEDV, SV, LVEF, CO, LVFS, EPSS, IVRT, A', Sm, and the positive predictive values were higher than the single diagnostic test (85.45%, 93.91%, 96.72%, 94.74%, 89.43%, 98.00%, 92.00%, 99.42%, 93.60%, respectively), the negative predictive values were lower than the single diagnostic test (50.89%, 57.93%, 49.15%, 58.18%, 57.05%, 45.74%, 57.92%, 64.13%, 47.78%, respectively). Conclusion:Cardiac ultrasound indicators LVEDV, SV, LVEF, CO, LVFS, EPSS, IVRT, A', and Sm combined with H-FABP are of certain value in the diagnosis of sepsis-associated heart dysfunction.
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Objective To examine the effect and mechanism of different targets of glucose control on liver damage in rats with sepsis .Methods The rat sepsis model was established by cecal ligation and puncture (CLP) .Forty Sprague‐Dawley rats were randomly divided into five groups (eight rats to each group):sham operation (sham group) ,sepsis (CLP group) ,glycemic control A group (glucose target 4 .6‐6 .1 mmol/L ) ,glycemic control B group (glucose target 6 .2‐8 .3 mmol/L ) and glycemic control C group (glucose target 8 .4‐10 .0 mmol/L) .The animals were sacrificed 12 hours after CLP .Venous blood was sampled for testing alanine transaminase (ALT ) , aspartate transaminase (AST ) and free fatty acid (FFA ) . Peroxisome proliferator activated receptor‐α (PPAR‐α) and liver carnitine palmitoyltransferase 1 (CPT‐1 ) protein were determined by immunohistochemistry .The pathological changes of liver tissue was observed under an optical microscope .Results The levels of ALT ,AST and FFA in venous blood and the pathological tissue injury score in sepsis groups were higher than those in sham group and all glycemic control groups (P0 .05) .The levels of PPARαand liver CPT‐1 were significantly higher in group A than in group B or group C (P<0 .05) ,and lower in group C than in group B(P<0 .05) .Conclusions The lowest target of glucose control(4 .6‐6 .1 mmol/L)shows better protective effects on liver damage in rats with sepsis ,the mechanism of which may be related to upregulation of PPARα and liver CPT‐1 expression .
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Objective To assess if the ratio of ApoB/ApoA1 is related to the metabolic syndrome and its components. Methods 709 adults living in Chongqing were enrolled. Weight, height, blood pressure, waist circumferences, fasting plasma glucose(FPG) , fasting serum insulin(FIns) and lipids were measured. ApoB/ApoA1 ratio, BMI and insulin resistance index were calculated. Results ApoB/ ApoA1 ratio was increased in subjects with insulin resistance(IR)and MS. Compared with the low ApoB/ ApoA1 ratio group, the high ApoB/ApoA1 ratio group was more likely to get MS(OR=3.5)and IR(OR =2.3) (P<0.001). Conclusions ApoB/ApoA1 ratio is strongly associated with IR, MS and its components, and a high ApoB/ApoA1 ratio is a valuable marker of MS.
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Objective To compare the analgesic efficacy and side effects of patient-controlled intravenous analgesia (PCIA) with Lornoxicam and patient-controlled epidural analgesia(PCEA) with morphine in patients undergoing Orthopaedics surgery. Methods 100 ASA Ⅰ-Ⅱ Patients scheduled for Orthopaedic surgery were divided randomly into two groups: Lornoxicam PCIA group( n =50) , Lornoxicam 48mg was diluted to 100ml with normal saline (0.9%NS). Morphine PCEA group( n =50), Morphine 9mg + bupivacaine 150mg were diluted to 100ml with normal saline (0.9%NS) .In both groups the patients were received PCA at a rate of 2ml/h with the bolus dose of 0.5ml and lockout interval of 15min. The loading dose was Lornoxicam 8mg plus Ondansetron 4mg in group PCIA and morphine 1mg and Ondansetron 4mg diluted to 10ml with normal saline (0.9%NS) in group PCEA 30 minutes before the end of operation. BP, RR, ECG, SpO_2 were monitored continuously after operation. Efficacy of analgesia was assessed by VAS scores. Side effects such as drowsiness, sweat, nausea, vomiting and skin pruritus were also observed. Results There was no significant difference in the mean VAS score between group PCIA and group PCEA at 4h, 8h, 16h ,20h, 24h, 32h and 48h. after operation. There was no significant difference in side effects between the two groups except the occurrence of sweat, nausea, vomiting and skin pruritus which was lower in group PCIA than in group PCEA ( P