OBJECTIVETo investigate the significance of changes in plasma high mobility group box-1 protein (HMGB1) levels and its relationship with sepsis and endotojemia in severely burned patients.

METHODSTotally 25 large area burned patients ( > 30% total body surface area) were included in this study, and 8 healthy volunteers served as normal controls. The plasma levels of HMGB1 were measured by ELISA, and endotoxin concentrations was determined by the modified chromogenic limulus amebocyte lysate (LAL) assay on posthurn days 1, 3, 5, 7, 14, 21, and 28.

RESULTSThe plasma HMGBL levels were markedly elevated on postburn day 1 in severely burned patients, and they were significantly higher in septic patients than those without sepsis on days 7, 21, and 28 after burns (P<0.05). Among septic patients, plasma HMGBI levels in the survival group were significantly lower than those with fatal outcome on days 3 and 21 (P<0.05, P<0.01). No significant correlations were found between HMGB1 levels and the sizes of total body surface area (P>0.05). In addition, the plasma HMGB1 levels were positively correlated with endotoxin concentrations on days 3, 5, 7, 21 after major burns (P<0.05, P<0.01).

CONCLUSIONSHMGB1, as an important late mediators of inflammation, may be involved in the development of sepsis following extensive burns, and it can be markedly induced by endotoxemia secondary to acute insults. Dynamic measurements of circulating HMGB1 levels should be helpful to monitor the disease course and judge the prognosis of burned patients.

Burns ; blood ; microbiology ; Endotoxins ; blood ; HMGB1 Protein ; blood ; Humans ; Sepsis ; blood

OBJECTIVETo evaluate the value of high mobility group box 1(HMGB1) in the diagnosis of pediatric acute appendicitis.

METHODSThe children with acute abdomen who had a diagnosis of suspected acute appendicitis between January and July 2013 and 25 healthy children were enrolled in this study. Serum HMGB1 levels were measured using ELISA on admission. The patients were classified into 2 groups according to surgery confirmation or pathological results: appendicitis (n=28) and non-appendicitis (n=35).

RESULTSSerum HMGB1 levels and WBC in the appendicitis and non-appendicitis groups were significantly higher than in the healthy children group (P<0.01). The appendicitis group showed more increased serum HMGB1 levels compared with the non-appendicitis group (median: 32.9 ng/mL vs 22.0 ng/mL; P<0.01). For a diagnosis of acute appendicitis, the sensitivity and specificity of serum HMGB1 was 71.4% and 82.9% respectively at the best cutoff of 28.0 ng/mL, with the accuracy of 77.8% and the area under the curve of 0.765 (95%CI 0.638-0.893).

CONCLUSIONSHMGB1 may play a role in the diagnosis of pediatric acute appendicitis.

Acute Disease ; Appendicitis ; blood ; diagnosis ; Child, Preschool ; Female ; HMGB1 Protein ; blood ; Humans ; Infant ; Male

OBJECTIVETo study the association between serum level of high-mobility group box 1(HMGB1) and neonatal respiratory distress syndrome (NRDS).

METHODSA total of 35 infants with NRDS and 35 normal neonates (control group) were enrolled. Peripheral venous blood samples were collected with 12-24 hours after birth. ELISA was used to measure the serum level of HMGB1.

RESULTSThe infants with mild and severe NRDS had a significantly higher serum level of HMGB1 than the control group (P<0.05). The infants with severe NRDS had a significantly higher serum level of HMGB1 than those with mild NRDS (P<0.05). The infants with NRDS who died had a significantly higher serum level of HMGB1 than those who survived (P<0.05). The receiver operating characteristic (ROC) curve showed that the optimal cut-off value for serum level of HMGB1 to predict NRDS was 625.3 pg/mL with an area under the ROC curve (AUC) of 0.846 (95%CI: 0.755-0.936), and the optimal cut-off value for serum level of HMGB1 to predict the death of infants with NRDS was 772.2 pg/mL with an AUC of 0.916 (95%CI: 0.813-1.000).

CONCLUSIONSInfants with NRDS have a significant increase in the serum level of HMGB1, and the serum level of HMGB1 can well predict the development and prognosis of NRDS.

Female ; HMGB1 Protein ; blood ; Humans ; Infant, Newborn ; Male ; Prognosis ; Respiratory Distress Syndrome, Newborn ; blood ; diagnosis

BACKGROUNDSepsis is a leading cause of death in the intensive care units. The late inflammatory cytokine, high-mobility group box 1 (HMGB1), plays a critical role in sepsis. In the present study, we investigated the association between the serum HMGB1 levels and the severity of organ injury in the lipopolysaccharide-induced sepsis in rats.

METHODSTo produce an animal model of sepsis with different degree of organ injury, animals were treated with three different doses of lipopolysaccharide (4, 8 and 16 mg/kg), and the animals in control group were treated with the same volume of the vehicle (saline). The levels of serum HMGB1 were measured at 0, 2, 4, 8, 16, 24, 32 and 48 hours after lipopolysaccharide (LPS) or vehicle injection, meanwhile the biochemical and histopathological indicators for the severity of organ injury were assessed.

RESULTSThe level of HMGB1 had a positive, high correlation with the abnormal changes of serum cardiac troponin I, alanine aminotransferase, aspartate aminotransferase, creatinine and blood urea nitrogen, as well as the pathologic scores of heart, lung, liver and kidney.

CONCLUSIONSThe level of serum HMGB1 is highly correlated with the severity of sepsis in rats, suggesting that HMGB1 could serve as a valuable adjunct in the diagnosis and management of sepsis.

Animals ; HMGB1 Protein ; blood ; Lipopolysaccharides ; therapeutic use ; Male ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Sepsis ; blood ; drug therapy ; pathology

OBJECTIVETo investigate the changing laws of serum high mobility group box 1 protein (HMGB1) in septic rats and intervention effect of Xuebijing on it.

METHODSLipopolysaccharide (LPS) (5 mg/kg BW) was intravenously injected into the tail vein of healthy male Wistar rats to prepare the sepsis rat model. In Experiment 1: 50 Wistar rats were randomly divided into three groups, i.e., the normal group (A, n=10); the LPS model group (B, n=10), the LPS +Xuebijing treatment group (C, n=30). Rats in the C group were further divided into three subgroups, i.e., 2 h before LPS injection (group C1), 2 h after LPS injection (group C2), and 8 h after LPS injection (group C3), 10 in each group. Blood samples were collected from the caudal vein to detect serum HMGB1 levels by Western blot at 4, 12, 24, 48, and 72 h after LPS injection. Experiment 2: 30 Wistar rats were equally divided into the LPS model group (D) and the LPS + Xuebijing treatment group (E), 15 in each group. They were treated as rats in the B group and the C1 group respectively. Five rats were sacrificed at 12, 24, and 48 h after LPS injection in the two groups. Blood as well as the tissue samples were harvested to measure such indices as ALT, AST, Cr, and BUN, as well as pathological changes of liver, lung, and kidney.

RESULTS(1) Compared with the A group, serum HMGB1 levels were higher at various time points in the B group (P < 0.05). Compared with the B group, serum HMGB1 levels at 12,24,48, and 72 h decreased in the C1, C2, and C3 groups. Besides, the decrease was more obvious at 24 h and 48 h.The decrement in the C3 group was less than that in the C1 and C2 groups (P < 0.05). (2) In the D group, ALT, AST, Cr, and BUN were significantly higher than those in the A group and reached the peak at 24 h (P < 0.05). Compared with the E group, AST, Cr, and BUN at 24 and 48 h, and ALT at each time point decreased significantly in the E group (P < 0.05). (3)The results of pathological section of liver, lung, and kidney showed local congestion and hemorrhage, cell edema/necrosis/degeneration, infiltration of inflammatory cells, damage of characteristic structures and so on; particularly serious lesion occurred at 24 and 48 h in the D group. The microscopic lesion was obviously alleviated in the E group than in the D group at corresponding time points.

CONCLUSIONSThe serum HMGB1 levels increased in septic rats, with late occurrence of peak value and longer duration of the high value. HMGB1 played an important role in excessive inflammatory response and multiple organ dysfunction. Xuebijing could reduce the serum levels of HMGB1, improve biochemical parameters, and attenuate severe inflammatory response of liver, lung, and kidney tissues in septic rats. Besides, the earlier use, the better effect obtained.

Animals ; Disease Models, Animal ; Drugs, Chinese Herbal ; therapeutic use ; HMGB1 Protein ; blood ; Male ; Rats ; Rats, Wistar ; Sepsis ; blood ; drug therapy

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 T_low>T_high (χ²=9.470, P<0.05), and for OS T_low>T_high (χ²=7.808, P<0.05); there was no difference in the survival of sRAGE high expression group and low expression group, for PFS T_lowhigh (χ²=1.661, P>0.05), and for OS T_lowhigh (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.
Enzyme-Linked Immunosorbent Assay ; HMGB1 Protein/blood* ; Humans ; Multiple Myeloma/therapy* ; Prognosis ; Receptor for Advanced Glycation End Products/blood*

OBJECTIVETo study both the release of HMGB1 from irradiation-treated mesenchymal stem cells (MSCs) and the effects of HMGB1 on human cord blood CD34(+) hematopoietic progenitor cell proliferation and differentiation.

METHODSMSCs were obtained from human bone marrow. HMGB1 released by the MSCs after treatment with 12 Gy gamma-ray irradiation was determined by enzyme linked immunosorbent assay (ELISA). CD34(+) cells were positively selected with a MACS CD34 isolation kit. The freshly isolated CD34(+) cells were cultured in the presence of HMGB1 for 6 days. Phenotype of cultured cells surface molecules (CD13, CD14, CD11c, CD41 and CD71) were analyzed by flow cytometry. The proliferation and differentiation capacities of cord blood HSCs were assayed by colony forming cell assay. The receptors of HMGB1 (RAGE, TLR2 and TLR4) on cord blood CD34(+) cells were detected by flow cytometry.

RESULTSHMGB1 level in the supernatant \[(4.3 +/- 0.9) ng/ml\] of the irradiated MSC was significantly higher than that in control \[(0.4 +/- 0.2) ng/ml\] (P < 0.01). Human cord blood CD34(+) cells expressed the HMGB1 receptors RAGE, TLR2 and TLR4. The HMGB1-treated CD34(+) cells contained higher proportions of CD13(+) \[(32.6 +/- 5.9)% vs (18.4 +/- 3.8)%\], CD14(+)\[(25.4 +/- 4.4)% vs (12.6 +/- 2.7)%\], CD11c(+) \[(20.3 +/- 3.9)% vs (9.8 +/- 2.1)%\], CD71(+) \[(47.1 +/- 7.4)% vs (26.6 +/- 4.6)%\] cells compared with control group did. But HMGB1 did not induce the generation of CD41(+) cells \[(1.3 +/- 0.5)% vs (1.1 +/- 0.4)%\]. Furthermore, HMGB1 profoundly induced the growth of BFU-E, CFU-GM and total CFU in a dose-dependent manner, and this effect was partially inhibited by TLR2 and TLR4 antibodies.

CONCLUSIONHuman MSC treated with gamma-ray irradiation can release HMGB1, which can induce the proliferation and differentiation of human cord CD34(+) cells.

Antigens, CD34 ; metabolism ; Cell Differentiation ; Cells, Cultured ; Fetal Blood ; cytology ; HMGB1 Protein ; Hematopoietic Stem Cells ; cytology ; Humans

OBJECTIVETo determine the expression of high-mobility group protein box 1 (HMGB1), high-sensitivity C-reactive protein (hs-CRP), and D-dimer (D-D) in the peripheral blood of children with Henoch-Schönlein purpura (HSP) and to investigate the clinical significance of HMGB1 in children with HSP.

METHODSA total of 40 children with HSP (HSP group) and 30 healthy children (control group) were involved in the study. The level of serum HMGB1 was determined using enzyme-linked immunosorbent assay, and the levels of serum hs-CRP and plasma D-D were determined using automatic biochemical analyzer and automatic blood coagulation analyzer, respectively.

RESULTSThe levels of HMGB1, hs-CRP, and D-D in the peripheral blood of the HSP group in the acute phase were significantly higher than in the control group (P<0.05). The levels of the three indicators were significantly higher in HSP children with renal damage than in those without renal damage (P<0.05). In children with HSP, the expression of HMGB1 was positively correlated with the expression of hs-CRP and D-D (r=0.878, P<0.001; r=0.625, P<0.001).

CONCLUSIONSThe expression of HMGB1 is related to the inflammatory response and hypercoagulability in children with HSP. HMGB1 may be involved in the development of HSP and associated renal damage in children.

C-Reactive Protein ; analysis ; Child ; Child, Preschool ; Female ; Fibrin Fibrinogen Degradation Products ; analysis ; HMGB1 Protein ; blood ; Humans ; Male ; Purpura, Schoenlein-Henoch ; blood

OBJECTIVETo investigate the changes in serum level of high mobility group protein B1 (HMGB1) in patients with delayed encephalopathy after acute carbon monoxide poisoning and the clinical significance of these changes.

METHODSThirty-four patients with delayed encephalopathy after acute carbon monoxide poisoning (delayed encephalopathy group), 30 normal controls (control group), and 32 cases of acute carbon monoxide poisoning without delayed encephalopathy (carbon monoxide poisoning group) were recruited in this study. The serum HMGB1 level was determined by enzyme-linked immunosorbent assay. The correlation between serum HMGB1 level and scores of the activity of daily living scale (ADL), Information-Memory-Concentration Test (IMCT), and Hasegawa dementia scale (HDS) was determined.

RESULTSIn the acute stage of carbon monoxide poisoning, the serum HMGB1 level of delayed encephalopathy group was significantly higher than those of the carbon monoxide poisoning group and the control group (P < 0.01). In the delayed encephalopathy group, serum HMGB1 level in the convalescent stage was significantly lower than that in the acute stage (P < 0.05); ADL score was higher and HDS and IMCT scores were lower in the acute stage than in the convalescent stage (P < 0.01). In the delayed encephalopathy group, serum HMGB1 level was positively correlated with HDS and ADL scores in both acute stage and convalescent stage (correlation coefficients: 0.612, 0.607, 0.609, and 0.612, P < 0.01).

CONCLUSIONHMGB1, as an important late mediator of inflammation, is involved in the inflammatory reaction in delayed encephalopathy, and is positively correlated with HDS and ADL scores, indicating that it can be used as one of the major indicators in monitoring carbon monoxide poisoning.

Adult ; Aged ; Aged, 80 and over ; Brain Diseases ; blood ; etiology ; Carbon Monoxide Poisoning ; blood ; complications ; Female ; HMGB1 Protein ; blood ; Humans ; Male ; Middle Aged

OBJECTIVETo investigate the change in T cell-mediated immunity and its relationship with plasma high mobility group box-1 protein (HMGB1) levels in severely burned patients.

METHODSThirty-five extensively burned patients (> 30% total body surface area) were included in this study, and were divided into MODS group (n = 13) and non-MODS group (n = 22). The blood samples were collected on post burn days 1, 3, 5, 7, 14, 21 and 28. The plasma levels of HMGB1 were measured by using ELISA, and T lymphocyte proliferation response and its IL-2 production ability in peripheral blood were determined too. In addition, the ratio of CD4+/CD8+ T cells were detected by using flow cytometry.

RESULTSPlasma HMGB1 levels were markedly elevated on post burn day 1 in severely burned patients, and HMGB1 level was significantly higher in MODS group than in non-MODS group (P < 0.05). Lymph proliferation response and IL-2 production of T cells in peripheral blood, and the ratio of CD4+/CD8+ T cells in MODS group were markedly lower than those in non-MODS group on post burn days 1, 14, 21 and 28 (all P < 0.05). It indicated that plasma HMGB1 levels were negatively correlated to T cellular immune function parameters, including lymphocyte proliferation response, IL-2 production, and the ratio of CD4+/ CD8+ T cells in extensively burned patients (all P < 0.05).

CONCLUSIONSExtensive burns could lead to T cellular immune dysfunction, which appears to be associated with the development of MODS. HMGB1, as an important late mediators of inflammation, might be involved in the pathogenesis of suppression of T cell-mediated immunity in these patients.

Adolescent ; Adult ; Burns ; blood ; complications ; immunology ; Female ; HMGB1 Protein ; blood ; Humans ; Immunity, Cellular ; immunology ; Male ; Middle Aged ; Multiple Organ Failure ; etiology ; immunology ; T-Lymphocytes ; immunology