The Value of Serum HMGB1 and sRAGE in the Diagnosis, Efficacy Monitoring and Prognosis of Newly Diagnosed Multiple Myeloma / 中国实验血液学杂志

OBJECTIVE@#To evaluate the value of high mobility group protein B1 (HMGB1) and soluble receptor for advanced glycation end products (sRAGE) in the diagnosis, efficacy monitoring and prognosis of newly diagnosed multiple myeloma (MM) patients.@*METHODS@#Fifty newly diagnosed MM patients before and after chemotherapy and 50 hematological outpatients from October 2018 to May 2020 were selected. Enzyme linked immunosorbent assay (ELISA) was used to detect the serum HMGB1 and sRAGE levels of the patients. ROC was used to further analyze the efficacy of serum HMGB1 and sRAGE levels on the diagnosis of MM. At the same time, the serum levels of HMGB1 and sRAGE before and after chemotherapy were compared, and their values in the evaluation of curative effect of MM patients were analyzed. According to the mean values of serum HMGB1 and sRAGE, all the patients were divided into different groups, the clinical characteristics and survival status of the patients were compared.@*RESULTS@#Before treatment the serum HMGB1 level of the patients in MM group was higher than that in control group, while sRAGE level was lower (t=11.363,6.127, P<0.001). The AUC of serum HMGB1 and sRAGE in the MM patients was 0.955 and 0.811, respectively. After 3 courses of chemotherapy, HMGB1 level of the patients in CR group was lower than before chemotherapy, while in PD group was higher, as well as sRAGE level of the patients in PR group (P<0.05). There were significant differences in R-ISS stage, HGB, CRP, ESR, CD56, CD117, D13S319 deletion between HMGB1 high expression group and HMGB1 low expression group (χ2=3.920, 6.522, 6.65, 4.16, 3.945, 6.65, 4.16, P<0.05), while there were significant differences in ISS stage, CRP and CD56 between sRAGE low expression group (28 cases) and sRAGE high expression group (22 cases) (χ2=4.565, 4.711, 5.547, P<0.05). Kaplan-Meier survival analysis showed that the patients in HMGB1 low expression group had better survival condition, for PFS Tlow>Thigh (χ2=9.470, P<0.05), and for OS Tlow>Thigh (χ2=7.808, P<0.05); there was no difference in the survival of sRAGE high expression group and low expression group, for PFS Tlow<Thigh (χ2=1.661, P>0.05), and for OS Tlow<Thigh (χ2=2.048, P>0.05). Cox analysis showed that LDH and HMGB1 were the factors affecting the prognosis of the patients, and both of them affected PFS (HR=2.771, 95% CI: 1.002-7.662, P=0.049; HR=6.022, 95% CI: 1.689-21.470, P=0.006), while HMGB1 also affected OS (HR=4.275, 95% CI: 1.183-15.451, P=0.027).@*CONCLUSION@#The serum HMGB1 and sRAGE have certain auxiliary value for the diagnosis and curative effect monitoring of newly diagnosed MM patients, and serum HMGB1 is expected to be an auxiliary detection index for the prognosis of MM.

Mechanism of high mobility group protein B1 in lipopolysaccharide-induced acute lung injury/acute respiratory distress syndrome / 中华危重病急救医学

Objective:To investigate the role and possible pathogenesis of high mobility group protein B1 (HMGB1) in lipopolysaccharide (LPS)-induced acute lung injury/acute respiratory distress syndrome (ALI/ARDS).Methods:① In vivo, 24 SPFC57BL/6 male mice were randomly divided into normal control group, ALI/ARDS model group, ethyl pyruvate (EP) treatment group and EP control group, with 6 mice in each group. The ALI/ARDS model was established by intraperitoneal injection of 20 mg/kg LPS. Mice in normal control group and EP control group were intraperitoneally injected with the same amount of sterile normal saline. Then, mice in the EP treatment group and EP control group were intraperitoneally injected with 40 mg/kg HMGB1 inhibitor EP. After 6 hours, the mice were sacrificed and lung tissues were collected. The expressions of heparan sulfate (HS), syndecans-1 (SDC-1), heparanase (HPA) and matrix metalloproteinases-9 (MMP-9) in lung tissues were detected by immunofluorescence technique. Orbital blood of mice was collected and serum was extracted to detect the content of HMGB1 by enzyme linked immunosorbent assay (ELISA). ② In vitro, human umbilical vein endothelial cells (HUVECs) were randomly divided into 6 groups: normal control group, HUVECs damage group (treated with 1 mg/L LPS for 6 hours), HMGB1 group (treated with 1 μmol/L recombinant HMGB1 for 6 hours), HMGB1+EP group (treated with recombinant HMGB1 for 1 hour and then added 1 μmol/L EP for 6 hours), LPS+EP group (treated with LPS for 1 hour and then added 1 μmol/L EP for 6 hours), EP group (treated with 1 μmol/L EP for 6 hours). The expressions of HS, SDC-1, HPA and MMP-9 in endothelial cells were detected by immunofluorescence technique. Results:① In vivo, light microscopy showed that the alveolar space was thickened after LPS stimulation, and there were a large number of inflammatory cells infiltrating in the alveolar space. Compared with ALI/ARDS model group, the expressions of HS and SDC-1 in lung tissue of EP treatment group were significantly increased [HS (fluorescence intensity): 0.80±0.20 vs. 0.53±0.02, SDC-1 (fluorescence intensity): 0.72±0.02 vs. 0.51±0.01, both P < 0.05], and the expressions of HPA and MMP-9 were significantly decreased [HPA (fluorescence intensity): 2.36±0.05 vs. 3.00±0.04, MMP-9 (fluorescence intensity): 2.55±0.13 vs. 3.26±0.05, both P < 0.05]; there were no significant changes of the above indexes in EP control group. Compared with ALI/ARDS model group, the content of serum HMGB1 in EP treatment group decreased significantly (μg/L: 131.88±16.67 vs. 341.13±22.47, P < 0.05); there was no significant change in the EP control group. ② In vitro, compared with HMGB1 group, the expressions of HS and SDC-1 in HMGB1+EP group were significantly higher [HS (fluorescence intensity): 0.83±0.07 vs. 0.56±0.03, SDC-1 (fluorescence intensity): 0.80±0.01 vs. 0.61±0.01, both P < 0.05], and the expressions of HPA and MMP-9 were significantly lower [HPA (fluorescence intensity): 1.30±0.02 vs. 2.29±0.05, MMP-9 (fluorescence intensity): 1.55±0.04 vs. 2.50±0.06, both P < 0.05]; the expression of HS, SDC-1, HPA and MMP-9 had no significant changes in EP group. Conclusion:HMGB1 participates in LPS-induced injury of endothelial cell glycocalyx, leading to increased lung permeability, and inhibition of HMGB1 can alleviate lung injury.

Effects of silencing HMGB1 combined with docetaxel chemotherapy on the proliferation and apoptosis of prostate cancer cells and its action mechanism / 中华男科学杂志

Objective@#To investigate the effect of silencing the high-mobility group box-1 protein (HMGB1) combined with docetaxel (DTX) on the proliferation and apoptosis of PCa cells and its possible action mechanism.@*METHODS@#The expression of HMGB1 mRNA in different PCa cell lines and normal prostatic epithelial cells was detected by RT-qPCR. The PC-3 cells were transfected with different HMGB1 small interfering RNAs (si-HMGB1, si-HMGB1-2 and si-HMGB1-3), and the silencing effect was detected. The effects of different concentrations of DTX on the proliferation of the PC-3 cells was determined by MTT. Then the PC-3 cells were randomly divided into five groups: control (conventional culture), si-HMGB1-NC (si-HMGB1-NC transfection), si-HMGB1 (si-HMGB1-3 transfection), DTX (20 nmol/L DTX), and si-HMGB1+DTX (si-HMGB1-3+20 nmol/L DTX transfection), followed by measurement of the survival rate of the cells by MTT, their apoptosis rate by flow cytometry, and the expressions of HMGB1, B-cell lymphoma-2 (Bcl-2) and Bcl-2-associated X (Bax) proteins in different groups by Western blot.@*RESULTS@#The expression of HMGB1 mRNA in the PC-3 cells was the highest and the lowest after transfection with si-HMGB1-3. DTX inhibited the proliferation of the PC-3 cells at various concentrations. Compared with the control group, the si-HMGB1 and DTX groups showed significantly decreased A values, cell survival rates and HMGB1 and Bcl-2 expressions, but increased cell apoptosis rates and Bax expressions (P < 0.05). In comparison with the si-HMGB1 and DTX groups, the si-HMGB1+DTX group exhibited a remarkably decreased A value, cell survival rate and Bcl-2 expression, but increased cell apoptosis and Bax expression. The expression of the HMGB1 protein was markedly lower in the si-HMGB1+DTX than in the DTX group (P < 0.05).@*CONCLUSIONS@#Silencing HMGB1 combined with DTX chemotherapy can inhibit the proliferation and promote the apoptosis of PCa cells, which may be attributed to its regulatory effect on the expressions of the Bcl-2 family-related proteins.、.

Research progress on release mechanism of high mobility group protein B1 in acute respiratory distress syndrome / 中华危重病急救医学

High mobility group protein B1 (HMGB1), a highly conversed non-histone nucleoproteins with strong pro-inflammatory property, is one of the inflammatory mediator of the acute respiratory distress syndrome (ARDS). Numerous studies have confirmed that HMGB1 regulates ARDS by binding to receptor for advanced glycation end product (RAGE), Toll-like receptor (TLR) and etc. And it can significantly increase the mortality of ARDS. But the mechanism of HMGB1 release is still unclear. This study focuses on the HMGB1 release progress, which connected with Janus kinases/signal transducer and activator of transcription (JAK/STAT), nuclear factor-κB (NF-κB), Notch, inflammasome, tumor necrosis factor (TNF), mitogen-activated protein kinase (MAPK), reactive oxygen species (ROS), peroxisome proliferator-activated receptor (PPAR) and other signaling or dependent pathways in ARDS.

Study on the correlation of HMGB1 and coagulation disorder in severe heatstroke rats / 解放军医学杂志

Objective To explore the association between HMGB1 and coagulation disorder in severe heat stroke rats. Methods A total of 48 rats were randomized equally into 8 groups: Room temperature group (Sham), severe heatstroke (HS) re-cooling 0 h (HS-0 h), 3 h (HS-3 h), 6 h (HS-6 h), 9 h (HS-9 h), 12 h (HS-12 h), 18 h (HS-18 h), 24 h (HS-24 h) groups. Sham group rats were housed at room temperature of (25.0±0.5) ℃ and humidity of (50.0%±5.0%), while severe heatstroke group rats were kept in an incubator at a temperature of (39.5±0.2) ℃ and humidity of 60.0%±5.0%. Rats with the rectal temperature (Tr) reached 43 ℃ were defined as the onset of severe heatstroke, followed by transferring to the room temperature for natural cooling. The blood samples were collected at 0, 3, 6, 9, 12, 18 and 24 h after natural cooling. Prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), fibrinogen (Fib) were evaluated by clotting methods. HMGB1and thrombin-antithrombin (TAT) were detected by ELISA. Results A linear association between HMGB1 and PT was found (P0.05); a nonlinear association between HMGB1 and PLT was found (P0.05). Conclusions HMGB1 has a significant association with coagulation disorder in severe heat stroke rats. The mechanism needs to be further studied.

The effect of losartan on the inflammatory damage through HMGB1 in the hepatocytes stimulated by heat stress / 解放军医学杂志

Objective To explore the function of losartan on heat-stress induced high-mobility group protein B1 (HMGB1) mediated inflammatory damage in the hepatocytes. Methods Rats were randomized into three groups: sham group (without heat stress), heatstroke group (heatstroke induction followed by i.p. injection of normal saline) and heatstroke+losartan group (heatstroke induction followed by i.p. injection of 50 mg/kg losartan). The serum and liver tissue were harvested nine hours after heatstroke to invest the serum alanine aminotransferase (ALT) levels, liver myeloperoxidase (MPO) levels, liver pathological morphology, serum HMGB1 levels as well as the expression of interleukin(IL)-1β and IL-18 in the liver. In vitro, the HBL3A hepatocyte cell lines were divided into the sham group (without heat stress), heat stress group and heat stress +losartan group (10 μmol/L losartan added into the supernatant after heat stress). Nine hours after heat stress, the cell viability and the levels of supernatant lactate dehydrogenase, supernatant HMGB, cytoplasm and total HMGB1 were all examined. Besides, the level of activated caspase-1 in hepatocytes, supernatant IL-1β and IL-18, as well as the cellular level of reactive oxygen species (ROS), were detected. The effects of recombinant HMGB1 with concentration gradients and 0.2 mmol/L hydrogen peroxide on the levels of IL-1β, IL-18 and HMGB1 in the heat stress hepatocytes treated by losartan were observed. Results In vivo, liver damage occurred in the rats of the heatstroke group. Compared with the heatstroke group, the levels of serum ALT, liver MPO, serum HMGB1, liver tissue IL-1β and IL-18 decreased in the heatstroke+losartan group (P<0.05). In vitro, hepatocytes in the heat stress group were apparently damaged. Compared with the heat stress, the levels of cytoplasmic HMGB1, supernatant HMGB1, IL-1β and IL-18 decreased in the heat stress+losartan group, and the cell survival rate increased (P<0.05). In addition, the HMGB1 inhibitor also reduced the levels of IL-1β and IL-18 in heat stress group hepatocytes. And the supplementation with HMGB1 increased the levels of IL-1β and IL-18 in heat stress hepatocytes treated by losartan (P<0.05). Losartan reduced the level of reactive oxygen species in heat stress hepatocytes, and the supplementation with hydrogen peroxide increased the level of HMGB1 in heat stress hepatocytes treated by losartan (P<0.05). Conclusion Losartan decreased the heat-stress induced HMGB1 mediated inflammatory damage in the hepatocytes.

Effect of Whenshen Prescription on Hepatic Encephalopathy in Patients with HBV-related Hepatic Cirrhosis and Content of HMGB1/TLR4 / 中国实验方剂学杂志

Objective:To investigate the effect of Whenshen prescription on hepatic encephalopathy in patients with HBV-related hepatic cirrhosis and kidney Yang deficiency syndrome and the content of high-mobility group protein B1 (HMGB1) and Toll-like receptor 4 (TLR4). Method:The 66 patients treated in the Hospital of Chengdu University of Traditional Chinese Medicine from August 2013 to January 2015 were included. A prospective, parallel controlled design was used. The 66 cases were randomly divided into treatment group and control group according to 1:1 ratio, with 33 cases in each group.The control group was treated with comprehensive therapy, colon dialysis and placebo enema, while treatment group was treated with comprehensive therapy, colon dialysis and Whenshen prescription enema for 10 days. Finally, liver function, number connect test (NCT), digit-symbol test (SDT), awake time, the total effective rate and content of HMGB1 and TLR4 were analyzed. Result:There was no significant difference between two groups at baseline. The total effective rate in treatment group was 93.9%, which was higher than 72.7% in control group (PP1 and TLR4 in treatment group were lower than those in the control group. Conclusion:Whenshen prescription can significantly improve the clinical efficacy by inhibiting the contents of HMGB1 and TLR4.

Dual roles of immune cells and cytokines in hepatic ischemia reperfusion injury / 中华肝胆外科杂志

Ischemia-reperfusion injury is one of the main causes of complications related to liver transplantation, hepatectomy, trauma and hemorrhagic shock. The cells of ischemia and hypoxic injury release of injury-related molecular patterns, lead to the activation of immune cells and cytokine, which further aggravates the inflammatory response and enlarges the injury. It’s indicated that injury-related molecular patterns, liver resident immune cells and cytokines play a key role in promoting inflammation and liver ischemia-reperfusion injury. However, recent studies suggested that the ischemia cells and cytokines played acomplex role in this process. Relevant progresses were reviewed in this article.

Dual roles of immune cells and cytokines in hepatic ischemia reperfusion injury / 中华肝胆外科杂志

Ischemia-reperfusion injury is one of the main causes of complications related to liver transplantation, hepatectomy, trauma and hemorrhagic shock. The cells of ischemia and hypoxic injury release of injury-related molecular patterns, lead to the activation of immune cells and cytokine, which further aggravates the inflammatory response and enlarges the injury. It ' s indicated that injury-related molecular patterns, liver resident immune cells and cytokines play a key role in promoting inflammation and liver ischemia-reperfusion injury. However, recent studies suggested that the ischemia cells and cytokines played acomplex role in this process. Relevant progresses were reviewed in this article.

Role of HMGB1-RAGE / TLRs-NF-κB signaling pathway on bone mesenchymal stem cells transplantation therapy for lipopolysaccaride-induced coagulation disorder rats / 中华危重病急救医学

Objective To determine the effect of bone mesenchymal stem cells (BMSCs) in transplantation therapy for lipopolysaccharide (LPS)-induced coagulation disorder and the underlying mechanism of high mobility group protein B1-receptors for advanced glycation end products / Toll-like receptors-nuclear factor-κB (HMGB1-RAGE / TLRs-NF-κB) signaling pathway.Methods BMSCs of female Sprague-Dawley (SD) rats ageing 4-5 weeks old were extracted and cultivatedin vitro, and the fourth-passaged BMSCs phenotype was identified by flow cytometry for transplantation in the following experimental study. The rats were randomly divided into normal saline (NS) control group, LPS group, and BMSC group according to the random number table with 15 rats in each group. Coagulation disorders model was reproduced by injection of 1 mg/kg LPS via saphenous vein, and the rats in the NS control group was injected with equal volume NS. Those in the BMSC group were infused BMSC 0.5 mL containing 1×106 cells via tail vein at 2 hours after LPS injection, and the rats in other groups were injected with equal volume NS. Abdominal aorta blood was collected at 1, 3 and 7 days post operation. Coagulation indexes such as platelet count (PLT), platelet volume distribution width (PDW), mean platelet volume (MPV), plateletcrit (PCT), platelet large cell ratio (P-LCR), activated partial thromboplastin time (APTT), prothrombin time (PT), thrombin time (TT), international normalized ratio (INR), and fibrinogen (FIB) were determined. The mRNA levels and contents of HMGB1, RAGE, TLR2/4 and NF-κB were determined by real-time reverse transcription-polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA), respectively.Results ① The cells culturedin vitro were spindle shaped or flat. The fourth-passaged BMSCs phenotype was successfully identified by flow cytometry technology. ②Coagulation indexes: compared with NS control group, PLT, PCT and FIB in LPS group were significantly decreased, PDW, MPV, P-LCP, and INR were significantly increased, and APTT, PT, and TT were significantly prolonged from the first day. Furthermore, those in LPS group were gradually ameliorated with prolongation of LPS induction time. The coagulation function abnormality induced by LPS was reversed by BMSCs with significant difference at 1 day as compared with LPS group [PLT (×109/L):398.8±17.9 vs. 239.1±15.8, PCT (％): 0.35±0.04 vs. 0.23±0.06, FIB (g/L): 1.7±0.6 vs. 0.8±0.1, PDW (％):12.4±1.6 vs. 16.2±1.5, MPV (fl): 11.0±1.6 vs. 13.7±1.1, P-LCP (％): 13.0±2.1 vs. 15.3±2.7, INR: 1.52±0.17 vs. 1.82±0.19, APTT (s): 66.3±4.1 vs. 89.5±4.5, PT (s): 18.3±0.7 vs. 25.1±1.9, TT (s): 87.5±7.8 vs. 115.0±9.7, allP < 0.05], till 7 days. ③ HMGB1-RAGE / TLRs-NF-κB signaling pathway related molecules: compared with NS control group, the mRNA expressions and contents of HMGB1, RAGE, TLR2/4 and NF-κB were significantly increased in LPS group from the first day. However, the mRNA expressions and contents of the molecules in LPS group were gradually decreased with prolongation of LPS induction time. After BMSC intervention, the mRNA expressions and contents of molecules at 1 day were significantly lower than those of LPS group [HMGB1 mRNA (2-ΔΔCt): 10.77±0.04 vs. 24.51±3.69, HMGB1 content (μg/L): 0.48±0.01 vs. 0.95±0.06; RAGE mRNA (2-ΔΔCt): 11.57±1.11 vs. 18.08±0.29, RAGE content (μg/L): 0.73±0.04 vs. 1.37±0.06; TLR2 mRNA (2-ΔΔCt): 2.60±0.22 vs. 12.61±0.27, TLR2 content (μg/L): 0.81±0.03 vs. 1.59±0.09; TLR4 mRNA (2-ΔΔCt): 2.95±0.52 vs. 4.06±0.11, TLR4 content (μg/L):0.80±0.09 vs. 1.18±0.11; NF-κB mRNA (2-ΔΔCt): 1.29±0.06 vs. 7.79±0.25, NF-κB content (μg/L): 1.22±0.24 vs. 2.42±0.26, allP < 0.05], till 7 days.Conclusion BMSCs administration could ameliorate the coagulation function in LPS-induced coagulation disorder rats and these might be associated with HMGB1-RAGE / TLRs-NF-κB signaling pathway inhibition.

Clinical significance of high mobility group protein B1 in patients with severe pneumonia complicated with sepsis / 新乡医学院学报

Objective To investigate the clinical significance of the changes of serum level of high mobility group protein B1 (HMGB1) in patients with severe pneumonia complicated with sepsis.Methods Fifty patients with severe pneumonia complicated with sepsisin in Respiratory Intensive Care Unit(RICU) of Xinxiang Central Hospital from April 2014 to March 2017 were selected as observation group;while 50 healthy individuals were selected as control group.The patients in the observation group were divided into death group(n =32) and survival group(n =18) according to the prognosis.The serum levels of procalcitonin(PCT) and HMGB1 of patients in the observation group were detected on the 1st,3rd,7th day of patients hospitalized in the RICU,while the acute physiology and chronic health evaluation Ⅱ (APACHE lⅡ)scores of the patients were evaluated.The serum levels of PCT and HMGB1 of subjects in the control group were detected during physical examination.Results There was no statistic difference in the mean arterial pressure,oxygenation index,body temperature and total white cell count of patients between the death group and survival group(P ＞0.05).On the first day of patients hospitalized in the RICU,the serum levels of PCT and HMGB1 of patients in the observation group were significantly higher than those in the control group (P ＜0.05).The serum levels of HMGB1 and the APACHEⅡ scores of patients in the death group were significantly higher than those in the survival group at each time point(P ＜0.05).On the first day of patients hospitalized in the RICU,there was no statistic difference in the serum level of PCT of patients between the death group and survival group (P ＞ 0.05);the serum level of PCT of patients in the death group was significantly higher than that in the survival group at another time point (P ＜ 0.05).The serum level of HMGB1 of patients in the observation group was positively correlated with the PCT and APACHE Ⅱ score (r =0.562,0.460;P ＜0.05).Conclusion The serum level of HMGB1 in patients with severe pneumonia complicated with sepsis is increased;and the increase of serum level of HMGB1 in the death cases is more obvious than that in the survival cases.So it can be used to evaluate the patient's condition and judge the prognosis.

Influence of down-regulation of RAGE receptor on HMGB1 expression and the volume of transplanted tumor / 实用医学杂志

Objective To explore the down-regulation of advanced receptor for advanced glycation end products(RAGE)on expression of high mobility group protein B1(HMGB1)in glioma cells line and the volume change of transplanted tumor in nude mice. Methods HMGB1 expression in glioma LN229 cells line (divided into a control group and a study group) was observed by immunohistochemical assay and Western blot. The control group received normal saline,whereas the study group received RAGE receptor blocking agent FPS-ZM1. Expression of HMGB1 protein was detected by the same methods. The difference of the expression was examined by independent sample t test. 30 Nu/Nu nude mice were randomly divided into two groups;the above two kinds cell lines were injected into the same area of the left back of nude mice. Six weeks after injection ,the volume size was measured six times ,and the variance of repeated measurement data was used to analyze the difference of the volume change. Results HMGB1 protein was mainly expressed in the cytoplasm and nucleus. As compared with the control group,HMGB1 protein expression levels were decreased in the study group(P < 0.05),the growth rate of transplanted tumor in nude mice was significantly faster in the control group than in the study group ,the difference was statistically significant(P < 0.05). Conclusions The growth and invasion of HMGB1 protein may be involved in glioma by RAGE receptor. RAGE receptor blocker FPS-ZM1 can significantly reduce the expression of HMGB1 protein and inhibit the growth of transplanted tumor volume. It is expected to be used for the research on glioma cell apoptosis.

Clinical study on influence of Rheum officinale on serum high mobility group protein B1 in patients with severe acute pancreatitis / 重庆医学

Objective To observe the effect of rhubarb enema on serum level of high mobility group protein B1 (HMGB1) in patients with severe acute pancreatitis (SAP).Methods A total of 60 cases of patients with SAP in our hospital were collected from October 2014 to October 2016,and were randomly divided into the observation group and control group (30 cases in each group).Serum levels of HMGB1 were dynamically detected on the 1st,3rd and 5th day after admission.The acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ) was conducted.The recovery time of gastrointestinal function and time for continuous renal replacement therapy (CRRT) were observed.Results On the 1st day after admission,no statistically significant difference was found in serum level of HMGB1 between the two groups (P＞0.05).The serum level of HMGB1 in the observation group was obviously decreased on the 5th day after admission,which was lower than that in the control group,there was statistically significant difference(P＜0.05).In the observation group,the value of difference between serum level of HMGB1 on the 1st day after admission and that on the 3rd day after admission was significantly negatively related with the APACHE Ⅱ score on the 3rd day after admission(r=-0.604,P＜0.05).In the observation group,the remission time of abdominal pain and abdominal distension,first time of exhaust and defecation and time for CRRT were significantly shorter than those in the control group,there were statistically significant differences (P＜0.05).Conclusion Rhubarb could improvesymptoms and prognosis of patients with SAP through effectively inhibit the expression of HMGB1.

Experimental study on the expression of α-SMA and HMGB1 in silicotic fibrosismodel rats interfered by lumbricus / 中华劳动卫生职业病杂志

Objective@#To observe the expression of alpha smooth muscle actin (α-SMA) and high mo-bility group protein B1 (HMGB1) in silicosis model rats interfered by lumbricus.@*Methods@#45 rats were ran-domly divided into the control group, model group and group interfered by lumbricus. The silicosis model rats were established. The group interfered by lumbricus were intragastric administered with lumbricus decoction by the 4 ml/kg dose. The control group and model group were ig administered with the equal amount of normal saline. Each group were killed 5 rats on the 7th, 14th and 28th day. The lung tissues were stained with HE and Sirius red methods. The mRNA expressions of α-SMA and HMGB1 were determined with RT-PCR; The pro-tein levels of α-SMA and HMGB1 were determined with Western blotting.@*Results@#Compared with the control group, the expression levels of α-SMA and HMGB1mRNA and protein in lung tissue of model group were grad-ually increased in the 7th, 14th and 28th days, the difference was statistically significant (P< 0.01) . Compared with model group, the levels of α-SMA and HMGB1mRNA and protein in lung tissue of group interfered by lumbricus were gradually lowered in the 7th, 14th and 28th days, the difference was statistically significant (P<0.05, P<0.01) .@*Conclusion@#Lumbricus inhibits the collagen deposition and the formation of silicosis pulmo-nary fibrosis, which may be related to the inhibition of HMGB1 expression and activation of α-SMA in lung tis-sue.

The effect of necrostatin-1 on high mobility group protein-B1 in liver of rats with hemorrhagic shock / 中华急诊医学杂志

Objective To investigate the effect and mechanism of necrostatin-1 (Hec-1) on the level of HMGB-1 protein in liver of rats with hemorrhagic-traumatic shock.Methods A number of 96 male SD rats were divided into sham-operated group,dimethyl sulfoxide (DMSO) group and Nec-1 group (n=32in each) by randomized number method.Rat model of hemorrhagic-traumatic shock was made by fracture of femoral bone and tibia bone and exsanguination from femoral vein until 30 mmHg and maintained at 30-40 mmHg for 90 min,then the shed blood was transfused back with Ringer's solution.The rats in shamoperated group were only under anesthesia for separating and ligating blood vessels,without exsanguination to induce hemorrhagic shock and without replenishment with blood.Rats in Nec-1 group were given 1 mg/kg Nec-1 through femoral vein 5 min before replenishment with blood and Ringer' s solution,while the rats in DMSO group were given equal volume of DMSO solution instead.Eight rats in each group were sacrificed separately at 2 h,8 h,16 h and 24 h after replenishment.The serum and liver tissues of rats in each group were collected to detect serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST),and to observe the pathological changes in liver with hematoxylin-eosin (HE) staining.The level of HMGB-1 in serum was detected by using ELISA.The cytoplasm protein and total protein expressions of HMGB-1 were assessed by using western blot analysis.Results Compared with DMSO group,levels of serum ALT at 8 h (P ＜0.05),16 h (P ＜ 0.01) and 24 h (P ＜ 0.01) in Nec-1 group were significantly lower.Level of serum AST in Nec-1 group were lower compared with DMSO group at 8 h (P ＜ 0.01),16 h (P ＜ 0.01) and 24 h (P ＜0.01).Compared with DMSO group,levels of serum HMGB-1 at 8 h (P ＜ 0.05),16 h (P ＜0.01) and 24 h (P ＜ 0.01) in Nec-1 group were significantly lower.Under light microscopy and transmission electron microscope,hepatic lobule destroyed,the blood extravasated,the immunocyte infiltrated and cellular organelle destroyed were found.Compared with DMSO group,the level of HMGB-1 protein in cytoplasm protein in Nec-1 group were significantly decreased at 8 h (P ＜ 0.01),16 h (P ＜0.01) and 24 h (P ＜0.01).The level of HMGB-1 protein in total protein in Nec-1 group were significantly decreased 8 h (P ＜ 0.05) and 24 h (P ＜ 0.05).Conclusions Nec-1 can remarkably protect the liver of rats with hemorrhagic-traumatic shock,decrease the level of HMGB-1,and protect the hepatocyte effectively.

Role of alarmins high mobility group protein B1 in sepsis / 中华危重病急救医学

High mobility group protein B1 (HMGB1) is the most representative substance in the alarmins family, it is actively or passively release to extracellular by the activation of monocyte/macrophage and the dead cells, and then it stimulates the production of a variety of inflammatory mediators, and increases the organism's inflammatory response through relevant receptors signaling pathways. In recent years, its concentration can reflect the severity of inflammation and injury and was related to the prognosis, HMGB1 has won more and more attention in the development of sepsis. By reviewing the study of HMGB1 in sepsis pathogenesis, signal pathway and reversal measures, it was found that HMGB1 was considered as an important inflammatory mediators and warning signal involved in the pathogenesis of sepsis, and was become a new target in the treatment of sepsis. Further research on the role of HMGB1 in the pathogenesis of sepsis is needed in the future, and the development of new drugs combined with HMGB1 will be used in the study of HMGB1 in animal experiments.

Protective roles of pulmonary rehabilitation mixture in experimental pulmonary fibrosis in vitro and in vivo

Abnormal high mobility group protein B1 (HMGB1) activation is involved in the pathogenesis of pulmonary fibrosis. Pulmonary rehabilitation mixture (PRM), which combines extracts from eight traditional Chinese medicines, has very good lung protection in clinical use. However, it is not known if PRM has anti-fibrotic activity. In this study, we investigated the effects of PRM on transforming growth factor-β1 (TGF-β1)-mediated and bleomycin (BLM)-induced pulmonary fibrosis in vitro and in vivo. The effects of PRM on TGF-β1-mediated epithelial-mesenchymal transition (EMT) in A549 cells, on the proliferation of human lung fibroblasts (HLF-1) in vitro, and on BLM-induced pulmonary fibrosis in vivo were investigated. PRM treatment resulted in a reduction of EMT in A549 cells that was associated with attenuating an increase of vimentin and a decrease of E-cadherin. PRM inhibited the proliferation of HLF-1 at an IC50 of 0.51 µg/mL. PRM ameliorated BLM-induced pulmonary fibrosis in rats, with reduction of histopathological scores and collagen deposition, and a decrease in α-smooth muscle actin (α-SMA) and HMGB1 expression. An increase in receptor for advanced glycation end-product (RAGE) expression was found in BLM-instilled lungs. PRM significantly decreased EMT and prevented pulmonary fibrosis through decreasing HMGB1 and regulating RAGE in vitro and in vivo. PRM inhibited TGF-β1-induced EMT via decreased HMGB1 and vimentin and increased RAGE and E-cadherin levels. In summary, PRM prevented experimental pulmonary fibrosis by modulating the HMGB1/RAGE pathway.

Emerging role of high mobility group protein B1 in pulmonary fibrosis / 医学研究生学报

Pulmonary fibrosis , an important cause of pulmonary diseases , has no effective protective and therapeutic meas-ures.Recent studies showed high mobility group protein B 1 (HMGB1) has an important role in the development of pulmonary fibrosis and many HMGB1 antagonists can alleviate pulmonary fibrosis in animal models .This paper summarizes the structure , function, intra-cellular signal transduction of HMGB1, the expression change of HMGB1 in pulmonary fibrosis and HMGB1 targeted therapy in pulmo-nary fibrosis in order to provide an effective basis for clinical treatment of pulmonary fibrosis .

Protective effect of the use of Xuebijing injection during laparotomy on perioperative inflammatory response and organ function / 中华危重病急救医学

Objective To investigate the role of Xuebijing injection in inhibiting perioperative inflammatory responses and protecting the function of multiple organs.Methods A single-blind,randomized,parallel controlled trial was conducted.60 patients in the First Affiliated Hospital of Zhejiang University School of Medicine,aged 18 to 80 years,ASA grade Ⅰ-Ⅲ,undergoing elective abdominal surgery,were enrolled.The patients were randomly divided into the control group (n =30) and the treatment group (n =30).In the control group,after induction of anesthesia,a continuous infusion of 0.9％ normal saline (NS) 200 mL was given in a speed of 2 mL/min,while a continuous infusion of Xuebijing 2 mL/kg in 100 mL of 0.9％ NS was given at 2 mL/min in the treatment group after induction of anesthesia.The blood sample was drawn,and body temperature,routine blood test,C-reactive protein (CRP),liver and kidney function,fasting glucose (Glu),and serum interleukin-6 (IL-6),high mobility group protein B 1 (HMGB 1) levels were determined in all the patients before anesthesia (T1),at the end of operation (T2),12 hours after operation (T3),or at 5:00 am on the third day after operation (T4).At the same time the adverse reactions were recorded for evaluation of the safety of Xuebijing.Results After using Xuebijing injection,T3 body temperature and the T3-T1 temperature difference in treatment group were significantly lower than those of the control group(℃℃:36.70 ± 0.37 vs.37.38 ± 0.47,t＝6.199,P＝0.000; 0.07 ± 0.50 vs.0.85 ±0.58,t＝5.598,P＝0.000).Postoperative white blood cell count,neutrophil percentage,and CRP were significantly higher than those before the operation,but the differences between two groups were not statistically significant.Compared with the control group,alanine aminotransferase (ALT),aspartate transaminase (AST),total bilirubin (TBil) levels at T3 of treatment group were significantly reduced [ALT (U/L):17.56 ± 9.80 vs.88.60 ± 179.76,AST(U/L):27.53 ± 13.12 vs.84.16 ± 151.14,TBil(μ,mol/L):15.46 ± 9.79 vs.25.63 ± 25.33,all P＜0.05].Difference of conjugated bilirubin (CB),blood urea nitrogen (BUN),creatinine (Cr),Glu were not statistically significant between two groups.IL-6 showed an increasing trend after the operation in both groups,and IL-6 level (ng/L) at T2 of the treatment group was significantly lower than that of the control group (41.42 ± 59.74 vs.124.84 ± 119.66,t=3.405,P=0.001).The HMGB 1 level of two groups at T4 were lower than those at T1,but it decreased significantly only in treatment group (μg/L:22.03 ± 15.73 vs.45.09 ± 33.79,P＜0.05),and there was no significant difference between two groups.No serious adverse events occurred during the clinical trial.Conclusions Application of Xuebijing injection during anesthesia can significantly diminish postoperative inflammatory injury,which plays an important role in the protection of liver function,helps restore organ function and improve prognosis,and it is safe and effective.

Correlation of HMGB1 expression with the synthesis and secretion of IFN-γin the pulmonary artery smooth muscle cells in rat models of chronic obstructive pulmonary disease / 医学研究生学报

[Abstract ] Objective Chronic obstructive pulmonary disease (COPD) is closely related to pulmonary hypertension .This study was to investigate the correlation of the expression of high mobility group protein B 1 ( HMGB1) with its synthesis and secretion of interferon-γ( IFN-γ) in the distal pulmonary arterial smooth muscle cells ( PASMCs ) of COPD rats and its clinical significance . Methods We established COPD models in rats , primarily cultured and identified PASMCs , and detected the synthesis and secretion of cytokine in the PASMCs induced by cigarette smoke extract (CSE) and/or lipopolysaccharide (LPS).The PASMCs in the control, CSE, LPS, and CSE+LPS groups were cultured with anti-HMGB1 antibodies at 0.2 mL 1∶1000.At 12, 24, 48 and 72 hours of inter-vention, the expression of HMGB1 in the PASMCs was detected by Western blot and the concentrations of HMGB 1 and IFN-γin the cell culture supernatant were measured by ELISA , followed by a correlation analysis . Results Light microscopy manifested a peak -valley growth pattern or fusiform shape of the cells , which were identified as PASMCs by α-actin immunohistochemistry and immuno-fluorescence .Western blot and ELISA showed statistically significant differences in the expression of HMGB 1 and concentrations of cell supernatant HMGB1 and IFN-γat 12 hours between any two of the four groups (P0.05). Conclusion The expression level of HMGB1 was positively correla-ted with the synthesis and secretion of IFN-γin the distal PASMCs of the COPD model rats , and anti-HMGB1 antibodies provide a new in-tervention target for the clinical treatment of COPD and inhibition of its systemic inflammatory response .