1.Regulatory effect of emodin on platelet function in mice with late sepsis
Jingchun SONG ; Qingwei LIN ; Qingbo ZENG ; Xingping DENG ; Xiaomin SONG ; Lincui ZHONG
Journal of Medical Postgraduates 2017;30(7):709-714
Objective Secretion and aggregation dysfunction of platelets are closely related with uncontrollable septic inflammation and abnormal blood coagulation.This study was to investigate the effect of emodin on platelet aggregation (PA) and secretion in mice with late sepsis.Methods We randomly divided 111 healthy SPF male C57BL/6 mice into a sham operation (SO) group, a cecal ligation (CL) group, and an emodin (Em) group and treated those of the Em group intragastrically with emodin after cecal ligation.At 72 hours after operation, we recorded the survival rate of the mice, measured the platelet count and the levels of serum alanine aminotransferase (ALT) and creatinine (Cr), and detected the PA rate by aggregometry, the P-selectin level by flow cytometry, the serum 5-HT concentration by ELISA, and the expressions of Rab27 mRNA and protein by RT-PCR and Western blot, respectively.Results At 72 hours after cecal ligation, the survival rates in the SO, CL and Em groups were 100%, 60% and 66.7%, respectively.The platelet count was significantly decreased in the CL group as compared with that in the SO group ([461.00±64.77] vs [775.00±65.89]×109/L, P<0.05) but remarkably increased in the Em group ([635.20±83.57]×109/L) in comparison with that in the CL group (P<0.05);the levels of ALT and Cr were markedly higher in the CL than in the SO group (ALT: [194.02±31.85] vs [41.55±1.24] U/L, P<0.05;Cr: [1.94±0.29] vs [0.72±0.11] mg/dL, P<0.05), but lower in the Em (ALT: [162.56±31.51] U/L;Cr: [1.53±0.30] mg/dL) than in the CL group (P<0.05);the PA rate and serum 5-HT concentration were significantly reduced in the CL group as compared with the SO group (PA: [12.67±4.04] vs [43.33±2.89]%, P<0.05;5-HT: [13.18±2.31] vs [34.35±5.79] ng/L, P<0.05), but the former was remarkably elevated ([24.67±2.52]%) while the latter showed no significant difference in the Em group ([17.41±2.16] ng/L) as compared with the CL group (P<0.05);the P-selectin expression was markedly higher in the CL than in the SO group ([16.78±1.60] vs [2.33±0.14] %, P<0.05), but lower in the Em ([12.58±2.28] %) than in the CL group (P<0.05).No statistically significant differences were observed at 72 hours postoperatively among the SO, CL and Em groups in the expression Rab27b mRNA (1.85±0.04 vs 1.84±0.02 vs 1.87±0.29, P>0.05).The Rab27b protein expression was markedly lower in the CL and Em groups than in the SO group (0.093±0.015 and 0.140±0.026 vs 10.380±0.036, P<0.05) but with no significant difference between the former two groups (P>0.05).Conclusion Emodin can improve platelet count and aggregation, down-regulate the expression of P-selectin, protect the liver and kidney function, and reduce mortality from late sepsis.
2.Clinical research on heparin monitoring blood purification:comparison of heparinase-modified thromboelastography versus activated partial thromboplastin time(APTT)in continuous renal replacement therapy for critically ill patients
Qingbo ZENG ; Nianqing ZHANG ; Longping HE ; Qingwei LIN ; Biao LI ; Jingchun SONG
Chinese Journal of Clinical Laboratory Science 2023;41(12):895-899
Objective To investigate the clinical values of heparinase-modified thromboelastography(hmTEG)in heparin monitoring during continuous renal replacement therapy.Methods A total of 97 cases who were undergoing continuous renal replacement therapy(CRRT)in the intensive care unit of the 94th People's Liberation Army Hospital from Jan 2014 to Jun 2019 were enrolled in this stud-y.The patients were divided into TEG group and APTT group according to different means of heparin monitoring during continuous renal replacement therapy.In total,278 hemofilters were used in all the blood purification therapies.Complication of bleeding,CRRT time,total heparin dose and SOFA(sequential organ failure assessment)score of the patients were compared between the TEG and APTT groups.The filter life span and survival time in hospital were also compared using Kaplan-Meier analysis.Rusults Compared with APTT group,the total heparin dose in TEG group were significantly higher(P<0.05).The CRRT time of patients and the average filter life span in TEG group were significantly longer than those of APTT group(P<0.05).Compared to APTT group,the 28-day SOFA in TEG group was significantly lower(P<0.05).Survival analysis showed that the 28-day risk of death in the patients of APTT group was 2.01 times higher than that in TEG group(P<0.05).The 72-hour filter life of TEG group was significantly longer than that of APTT group(P<0.05).Conclusion The use of hmTEG for monitoring heparin in blood purification should be superior in terms of safety and efficacy with longer filter life span and higher survival rate of patients.
3.Prognostic value of thrombomodulin in patients with septic shock
Qingbo ZENG ; Nianqing ZHANG ; Longping HE ; Hailin GONG ; Fang WANG ; Jingchun SONG
Chinese Journal of Clinical Laboratory Science 2024;42(6):436-440
Objective To investigate the prognostic value of plasma thrombomodulin(TM)in patients with septic shock.Methods A retrospective analysis was conducted on the clinical data of 180 patients with septic shock admitted to the intensive care unit of the 908th Hospital from May 2018 to November 2022.The patients were divided into survival group(106 cases)and death group(74 ca-ses)based on the 30-day follow-up outcomes.Propensity score matching(PSM)was used to match 57 surviving patients with 57 de-ceased patients in a 1∶1 ratio,based on confounding factors such as age,gender,underlying diseases,primary infection site,laborato-ry results and disease severity scores.TM and other coagulation molecular markers were compared between the two groups,and logistic regression,receiver operating characteristic(ROC)curve,survival and correlation analyses were performed.Results After PSM,the TM levels in the death group(18.3[13.2,22.3]TU/mL)were significantly higher than those in the survival group(13.7[9.0,18.3]TU/mL)(P<0.05).Multivariate logistic regression analysis showed that TM was an independent risk factor for 30-day mortality in the patients with septic shock(OR=1.137,95%CI:1.023-1.262,P<0.005).ROC curve analysis revealed that the areas under the curve(AUCs)for predicting 30-day mortality were 0.665,0.627 and 0.600 for TM,Acute Physiology and Chronic Health EvaluationⅡ(APACHE Ⅱ)and Sequential Organ Failure Assessment(SOFA)scores,respectively.Kaplan-Meier survival analysis stratified by the optimal TM cut-off value(17.9 TU/mL)showed that the 30-day survival rate of the TM<17.9 TU/mL group was 1.56 times that of the TM≥17.9 TU/mL group(Log-Rank test,P<0.000 1).Spearman correlation analysis demonstrated that TM levels were positively correlated with APACHE Ⅱ(r=0.10,P<0.005)and SOFA scores(r=0.35,P<0.005).Conclusion Plasma TM has showed a good predictive value for assessing the prognosis of patients with septic shock and may serve as a potential biomarker for determining the prognosis of septic shock.
4.Value of thromboelastography in evaluating prognosis of polytrauma patients
Qingbo ZENG ; Jingchun SONG ; Qingwei LIN ; Jin XU ; Lincui ZHONG ; Xingping DENG ; Xiaomin SONG ; Xin ZHANG
Chinese Journal of Trauma 2019;35(3):254-258
Objective To investigate the value of thromboelastography ( TEG) in evaluating the prognosis of polytrauma patients. Methods A retrospective case control study was conducted to analyze the clinical data of 155 polytrauma patients admitted to 94th Hospital of People's Liberation Army from September 2015 to December 2017. There were 118 males and 37 females, aged 18-88 years [(49. 0 ± 1. 3)years]. Injury severity score (ISS) was (26. 4 ± 11. 0)points. According to the prognosis of patients 90 days after injury, the patients were divided into survival group ( 143 patients ) and death group (12 patients). The ISS on admission, acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ), Glasgow coma score ( GCS ) , systolic blood pressure ( SBP ) , respiratory rate ( RR ) and outcome of 90 days after injury were collected. Red blood cells( RBC) , hemoglobin( Hb) , plasma prothrombin time ( PT) , activated partial thromboplastin time ( APTT) , fibrinogen ( FIB) , international normalized ratio ( INR) , thrombin time ( TT) , platelet count ( PLT) and TEG-related indicators within 2 hours after ICU admission were collected. TEG-related indicators including TCG clotting reaction time ( R ) , clot formation rate (K), clot formation kinetics (α angle), maximum amplitude (MA), coagulation index (CI), blood clotting strength (G), elasticity constant (E) and clot lysis time (CLT) were collected within 2 hours after admission to ICU. The changes of TEG-related indicators were compared between the two groups, and logistic regression analysis and receiver operating characteristic ( ROC) curve analysis were performed. Results Compared with the survival group, ISS and APACHE II scores in the death group were significantly higher, while GCS, SBP, RR, RBC and Hb were significantly lower (P<0. 05). Compared with the survival group, death group showed significantly prolonged PT [(21. 1 ± 9. 1) s vs. (16. 5 ± 4. 3)s] as well as reduced FIB [(1. 7 ± 1. 5)g/L vs. (2. 7 ± 1. 7)g/L] (P<0. 05). Compared with the survival group, the K value in the death group was significantly prolonged [5. 2(1. 8,8. 0)min vs. 2. 9(2. 1,4. 2)min] (P<0. 05). Compared with the survival group, death group showed significant decrease in G value (3762. 4 ± 3346. 7 vs. 6366. 5 ± 3886. 1), E value (75. 3 ± 67. 0 vs. 127. 3 ± 77.7),αangle[(38.4±19.7)°vs. (49.4±16.6)°],MA[(37.4±17.5)mmvs.(52.0±13.3)mm], CI [-6. 8(-9. 5, 1. 5) vs. -2. 9 ( -5. 9, -0. 7)] and CLT [39. 2 (32. 5, 46. 9) min vs. 46. 4 (32. 7, 60.8) min] (P<0. 05). There were no significant differences in APTT, TT, INR, PLT and R between the two groups (P>0. 05). Logistic regression analysis showed that MA was significantly associated with the prognosis of polytrauma patients (OR=1. 15, 95% CI 1. 04-1. 28, P<0. 05). The area under the ROC curve of MA was 0. 756 (P <0. 05). When the MA threshold was 43. 1 mm, the sensitivity, specificity, positive predictive value and negative predictive value of predicted survival were 77. 5%, 76. 9%, 76. 1% and 97. 3%, respectively. Conclusion TEG index MA can determine the prognosis of polytrauma patients, and the mortality rate is significantly increased at MA<43. 1 mm.
5.Neutralization of interleukin-6 alleviates acute liver injury in mice
Yi ZENG ; Qingbo PAN ; Yanxi SHEN ; Hong REN
Chinese Journal of Hepatology 2020;28(6):509-514
Objective:To study the role of interleukin 6 (IL-6) in the occurrence and development of acute liver injury.Methods:Twelve C57BL/6 male mice without specific pathogens were randomly divided into a control group and an acute liver injury model group, with six mice in each group. Control and model group were injected with an equal volume (dosage of 10 mg/kg) of phosphate-buffered saline (PBS) and concanavalin A (ConA) into the tail vein, respectively. Samples were collected at 6 h for liver HE staining. Transaminase assay was used to determine the success of the induction model. The expression of IL-6, IL-17, IL-1β, interferon (IFN) γ and tumor necrosis factor α were screened by quantitative fluorescence PCR (qPCR). The expressional condition of IL-6 and IFNγ were measured by enzyme-linked immunosorbent assay (ELISA). Subsequently, three control groups and three IL-6 neutralizing antibody groups were established for acute liver injury, respectively. Equal volumes of PBS or IL-6 neutralizing antibody (100 μg/body) were injected prior 30 minutes, followed by injection of ConA (10 mg/kg) into the tail vein. Blood sampled from eye and liver tissue were fetched at 6 h. Liver tissues were stained with HE and serum alanine aminotransferase (ALT) was determined. An independent sample T-test was used for data comparison.Results:Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) of the model group was significantly higher than control group [ALT: (2 618.99 ± 188.08) U/L and (43.34 ± 5.02) U/L, t = -13.69, P = 0.001; AST: (942.48 ± 150.44) U/L and (57.80 ± 4.84) U/L, t = -5.878, P = 0.01]. Liver HE staining showed that the structure of hepatocyte cord was disordered, the cytoplasm of hepatocyte was lightly stained, and large necrotic foci were gradually formed, accompanied by lymphocyte infiltration, and then a mouse model of acute liver injury was successfully established. Protein levels of IL-6 and IFN, and mRNA of the model group were significantly up-regulated, as compared to control group. IL-6 mRNA expression of the model group was increased 73.7 times that of the control group ( t =-6.218, P < 0.001), and the serum IL-6 expression level was also higher than that of the control group (18 537.02 ± 92.57) pg/ml ( t = -199.782, P < 0.001). IFNγ mRNA was 108.4 times higher than that of the control the group ( t = -4.413, P = 0.003), and serum IFNγ concentration of the model group was also higher than the control group (12 068.30 ± 288.43) pg/ml ( t = -41.748, P < 0.001). Among them, IL-6 level was obviously increased, suggesting that it could participate in the occurrence and development of liver injury. IL-6 neutralizing antibody was injected into the tail vein. ALT level of IL-6 neutralizing antibody was significantly lower than acute liver injury control group [(167.41 ± 47.80) U/L and (1 520.34 ± 190.21) U/L, t = 6.899, P = 0.015]. Liver tissue HE staining showed that hepatocyte necrosis and the number of necrotic foci was significantly alleviated after blocking serum IL-6.Immunohistochemical results showed that the expression of activated caspase3 and hepatocyte apoptosis in the IL-6 neutralizing antibody group was decreased. Conclusion:Neutralizing IL-6 can significantly reduce acute liver injury caused by concanavalin A.