Sepsis is an infection induced systemic inflammatory response syndrome and is a major cause of morbidity as well as mortality in intensive care units. A growing body of evidence suggests that the activation of a proinflammatory cascade is responsible for the development of immune dysfunction, susceptibility to severe sepsis and septic shock. The present theories of sepsis as a dysregulated inflammatory response and immune function, as manifested by excessive release of inflammatory mediators such as high mobility group box 1 protein (HMGB1), are supported by increasing studies employing animal models and clinical observations of sepsis. HMGB1, originally described as a DNA-binding protein and released passively by necrotic cells and actively by macrophages/monocytes, has been discovered to be one of essential cytokines that mediates the response to infection, injury and inflammation. A growing number of studies still focus on the inflammation-regulatory function and its contribution to infectious and inflammatory disorders, recent data suggest that HMGB1 formation can also markedly influence the host cell-mediated immunity, including T lymphocytes and macrophages. Here we review emerging evidence that support extracellular HMGB1 as a late mediator of septic complications, and discuss the therapeutic potential of several HMGB1-targeting agents in experimental sepsis. In addition, with the development of traditional Chinese medicine in recent years, it has been proven that traditional Chinese herbal materials and their extracts have remarkable effective in treating severe sepsis. In this review, we therefore provide some new concepts of HMGB1-targeted Chinese herbal therapies in sepsis.

BACKGROUND:As the regulators of cytokines, suppressors of cytokine signaling (SOCS) play an important role in the inflammation reaction. Some studies found that SOCS-1 and SOCS-3 were involved in the pathogenesis of some inflammatory diseases such as rheumatoid arthritis, inflammatory bowel disease. But the expressions of SOCS in coronary heart disease have not yet been reported. This study aimed to investigate the expression and clinical significance of SOCS-1 and SOCS-3 in the myocardium of patients with sudden cardiac death (SCD).METHODS:Myocardial autopsy specimens were collected from 24 patients at the Forensic Medicine Department of Sun Yat-Sen University, Guangzhou, China between 2005 and 2006. Of them, 9 patients had autopsy findings consistent with coronary atherosclerosis (non-myocardial infarction) leading to SCD (non-MI group), 7 died of acute myocardial infaction (MI group), and 8 died from traffic accidents and trauma (control group). The expressions of SOCS-1 mRNA and SOCS-3 mRNA in the myocardium of the non-MI, MI and control groups were detected using RT-PCR. The levels of SOCS-1 and SOCS-3 proteins were detected using immunohistochemistry. Statistical analyses were performed using SPSS version 13.0 software and the data were analyzed by ANOVA.RESULTS:The expressions of SOCS-1 mRNA and SOCS-3 mRNA in the non-MI and MI groups were significantly higher than those in the control group[(0.788±0.101), (0.741±0.111) vs. (0.436±0.044), (P<0.01); (0.841±0.092), (0.776±0.070) vs. (0.454±0.076), (P<0.01)] respectively. The antibody-positive cells of SOCS-1 protein in the myocardium of the non-MI and MI groups were significantly higher than those in the myocardium of the control group[(320.00±48.48), (347.14±70.88) vs. (42.50±10.35), (P<0.01)] respectively. The antibody-positive cells of SOCS-3 protein in the myocardium of the non-MI and MI groups were significantly higher than those in the myocardium of the control group[(381.11±59.25) vs. (40.00±10.69), (P<0.01)] and[(332.86±111.91) vs. (40.00±10.69), (P=0.001)].CONCLUSION:The expressions of SOCS-1 and SOCS-3 in the myocardium of patients with SCD from coronary heart disease are significantly increased and contribute to the pathogenesis of SCD.

BACKGROUND:Measurement of the osmol gap (OG) is a technique that is used frequently in toxic alcohol poisonings (ethylene glycol (EG) and methanol) as a rapid means to estimate exposure, and can be performed in virtually all hospital laboratories. The value of the OG has not been previously evaluated for diethylene glycol (DEG) exposures. The primary objective of this study was to evaluate the utility of the OG in estimating DEG serum concentrations using the most common formula that is currently used for estimating methanol, ethanol, and ethylene glycol concentrations.METHODS:This was a controlled laboratory investigation using serum samples individually spiked with a known quantity of toxic alcohol compared to no toxic alcohol. Test samples were spiked with ethanol, DEG, EG, and methanol. Serum chemistries and osmolality and osmolarity were determined, and the OG was determined for each specimen.RESULTS:The percent error of estimating DEG concentrations of 26.3％ was similar to the mean percent error for estimating other alcohol concentrations, 30.5％±5.6％ (P>0.05, 95％ confidence interval 16.7％-44.3％).CONCLUSIONS:The severity of metabolic effects associated with DEG and the need to appropriately determine rescue treatments mandate early detection of significant exposures for effective triage and patient management. Our results indicate that the percent error of the osmol gap method for estimating DEG concentration is similar to that of other toxic alcohols; this simple technique could be a valuable clinical tool, since quantitative DEG analysis is rarely available.

BACKGROUND:Hand-foot-mouth disease has become a major public health issue in children in China. In the present prospective study we investigated the clinical characteristics and emergency management of children with severe encephalitis associated with NPE caused by enterovirus 71. METHODS:The study was conducted in 2 pediatric intensive care units (PICUs) over a 2-month period. Clinical records were reviewed of critically ill children with severe encephalitis associated with NPE caused by EV71 who were admitted to PICUs during the period of May to June 2008 in Fuyang. RESULTS:We reviewed the complete records of 36 children, of whom 23 (63.9％) were male and 13 (36.1％) female. Their age ranged from 4 to 48 months, with an average of 15.8 months. Al children except one were under 3 years of age. The overal mortality in these children was 19.4％. The average duration of critical life threatening signs and symptoms was 2.1 days (12 hours-5 days). Nervous system diseases included brainstem encephalitis in 27 children (75％), brainstem encephalitis associated with myelitis in 6 children (16.7％), and general encephalitis in 3 chidren (8.3％), respectively. In 12 patients of NPE (33.3％) pink or bloody bubble sputum and asymmetric pulmonary edema or hemorrhage was the primary manifestation but no typical exanthema was observed. Five children died of acute onset of NPE and / or pulmonary hemorrhage with rapid progression of cardiopulmonary failure within hours after admission. Therapeutic management consisted of mechanical ventilation and administration of mannitol, methylprednisolone, intravenous immunoglobulin (IVIG) and vasoactive drugs, associated with the need of fluid volume resuscitation in 9 (25％) of the 36 children. CONCLUSIONS:In children less than 3 years of age found to be affected by severe EV71 encephalitis associated with NPE, one fifth may die. The major organ systems infected by severe EV71 include the central nervous system, the respiratory system, and the cardiovascular system. Early diagnosis and evaluation, respiratory support, treatment of intracranial hypertension, and mainttenance of function of the cardiovascular system are the most important therapeutic measures.

BACKGROUND:Kawasaki disease (KD) is a common cause of acquired heart disease in children. Recent studies have focused on the biochemical markers of the myocardium, their high sensitivity and specificity and significance in the diagnosis of KD. This study aimed to determine the serum level of brain natriuretic peptide (BNP) and its relation with the heart function of children with KD and to explore its clinical value in diagnosis of KD. METHODS:Forty-three KD children, aged from 5 months to 8 years (mean 2.3±0.6 years ), were admitted to Qingdao Children's Hospital from February 2007 to April 2009. Among them 27 were male, and 16 female. The 43 patients served as a KD group. Patients with myocarditis, cardiomyopathy, congenital heart disease and other primary heart diseases were excluded. Thirty healthy children, aged from 3 months to 15 years (mean 2.5±0.8 years) or 17 males and 13 females served as a control group. There were no significant differences in age and gender between the two groups (P>0.05). In the KD group, ELISA was used to measure the levels of serum BNP in acute and convalescent stages;and in the control group, the levels of serum BNP were measured once randomly. Left ventricular ejection fraction (LVEF), left ventricular shorten fraction (LVSF), cardiac index (CI) and left ventricular inflow velocity through the mitral annulus (including E-velocity and A-velocity) were measured by two-dimensional echocardiography in the acute and convalescent stages in the KD group. All data were expressed as mean±SD. The methods of analysis included Student's t test and the linear regression analysis test. P<0.05 was considered statistically significant. RESULTS:The level of serum BNP in the acute stage (517.26±213.40) ng/ml was significantly higher than that in the convalescent stage (91.56±47.97) ng/ml in the control group (37.55±7.56) ng/ml (P<0.01). The levels of LVEF, LVSF and CI in the acute stage were significantly lower than those in the convalescent stage (P<0.05), but the E/A level was not significantly different between the acute and convalescent stages (P>0.05). Linear regression analysis showed that the BNP level was negatively correlated with the levels of LVEF, LVSF and CI(r=-0.63, -0.52, -0.53, P<0.05) , but not significantly correlated with the E/A level (r=-0.18, P>0.05). CONCLUSION:The levels of serum BNP are significantly increased in KD patients, and are negatively correlated with the levels of LVEF, LVSF, and CI. The detection of serum BNP level is of clinical significance in the diagnosis of KD.

BACKGROUND:Stroke is the leading cause of death and long-term disability. This study was undertaken to investigate the factors influencing daily activities of patients with cerebral infarction so as to take interventional measures earlier to improve their daily activities. METHODS:A total of 149 patients with first-episode cerebral infarction were recruited into this prospective study. They were admitted to the Encephalopathy Center, Department of Neurology, the First Affiliated Hospital of Wenzhou Medical College in Zhejiang Province from August 2008 to December 2008. The baseline characteristics of the patients and cerebral infarction risk factors on the first day of admission were recorded. White blood cell (WBC) count, plasma glucose (PG), and many others of laboratory targets were col ected in the next morning. Barthel index (BI) was calculated at 2 weeks and 3 months respectively after onset of the disease at the outpatient clinic or by telephone cal . Lung infection, urinary tract infection and atrial fibrillation if any were recorded on admission. The National Institute of Health Stroke Scale (NIHSS) scores and the GCS scores were recorded within 24 hours on and after admission, at the second week, and at the third month after the onset of cerebral infarction respectively. RESULTS:The factors of BI at 2 weeks and 3 months after onset were the initial PG level, WBC count and initial NIHSS scores. Besides, urinary tract infection on admission was also the factor for BI at 3 months. CONCLUSION:Active measures should be taken to control these factors to improve the daily activities of patients with cerebral infarction.

BACKGROUND:With the development of industry and agriculture, organotin compounds have been widely used in China. Organotin compounds cause a common occupational poisoning. The toxicity of organotin was reported in animal studies; however the reports about human organotin intoxication are very rare. In this study we retrospectively analyzed the clinical manifestations of 15 organotin-poisoned patients who had been treated at our hospital from 2002 through 2007. METHODS:Fifteen patients with organotin poisoning were admitted to Sir Run Run Shaw Hospital Affiliated to Zhejiang University School of Medicine from 2002 to 2007. They were 9 males and 6 females, aged from 25 to 52 years. Clinical manifestations and Glasgow Coma Scales showed that the poisoning was mild in 4 patients, moderate in 6 and severe in 5. The severe patients were given glucocorticoid after hospitalization by intravenous guttae of 500 mg methylprednisolone for the first day, followed by 160 mg methylprednisolone per day for three days, and then 80 mg methylprednisolone per day for another three days. Potassium glutamate and sodium glutamate were intravenously dripped to reduce blood ammonia; intravenous guttae plus oral administration of potassium 9 g/day was used to correct intractable hypokalemia; sodium bicarbonate was used to correct metabolic acidosis, and sedatives were used to control spasm and twitch; mechanical ventilators were used in 4 patients with dyspnea. RESULTS:Most of the patients showed elevated level of blood ammonia, decreased level of blood potassium and metabolic acidosis, but some had demyelination changes shown by CT and MRI. Treatments included correction of metabolic acids, blood potassium and ammonia, and mechanical ventilation when necessary. For patients with injuries of the nervous system, glucocorticoids were given immediately after hospitalization. These patients showed intractable hypokalemia and metabolic acidosis during the treatment. Forteen patients recovered completely without long-term side-effect. One patient in the aphasiac stage restored the linguistic capacity during a 6-month follow-up. CONCLUSIONS:Elevated level of blood ammonia, decresed level of blood potassium, and metabolic acidosis are common in patients with organotin poisoning. Demyelination can be observed in patients with severe poisoning. The abnormalities of the patients are reversible after suitable treatments.

BACKGROUND:Development of new coronary thrombolytic agents is hot in the market. A new drug, mutated recombinant tissue-type plasminogen activator (rtPAm), is the product of mutation of tPA by changing binding loci with plasminogen activator inhibitor (PAI)-1 to reduce the degradation. In vitro test has demonstrated that the activity of rtPAm is much higher than rtPA in the absence of PAI. The present study is to observe the efficacy of mutated recombinant tissue-type plasminogen activator (rtPAm) in coronary thrombolytic therapy. METHODS:A total of 30 adult beagles were equally divided into 5 groups after thrombi:vehicle group, urokinase group, rtPAm low-dose group, rtPAm medium-dose group, and rtPAm high-dose group. Thrombolytic effect and myocardial infarction were observed after thrombolytic therapy. RESULTS:In the urokinase group, time to reperfusion was (15.8±3.8) minutes. TIMI 2 flow was demonstrated in 4 beagles, TIMI 3 flow in 2, and re-occlusion in 4 after 90 minutes respectively. In the low-dose rtPAm group, time to reperfusion was (15±4.5) minutes; TIMI 2 flow was demonstrated in 2 beagles, TIMI 3 flow in 4, and re-occlusion in 2 after 90 minutes. In the high-dose rtPAm group, time to reperfusion was (7.5±2.6) minutes. None of the beagles showed re-occlusion after 90 minutes. The infarction areas were (2.1+0.9)％ in the medium-dose rtPAm group and (0.7+0.4)％ in the high-dose rtPAm group, which decreased significantly than those in the low-dose rtPAm group. The aggregation rate in the medium-dose and high-dose rtPAm groups decreased significantly than that in the urokinase group. CONCLUSION:rtPAm may serve as a thrombolytic agent with platelet-targeted fibrinolysis and antiplatelet aggregation activities.

BACKGROUND:Recent studies have shown that α2-adrenergic agonists can reduce postresuscitation myocardial injury. This study was undertaken to observe changes of hemodynamics, myocardial injury markers cTnT and cardiac morphology by establishing a cardiopulmonary resuscitation model with rabbits, and to detect whether α-methyl norepinephrine (α-MNE) can reduce the myocardial injury after CPR and improve cardiac function. METHODS:Eighteen health rabbits, weighing 2.5-3.5 kg, both male and female, were provided by the Lanzhou Institute of Veterinary Medicine. After setting up a rabbit model of cardiopulmonary resuscitation, 18 rabbits were randomly divided into three groups. The rabbits in group A as an operation-control group were subjected to anesthesia, endotracheal intubation, and surgery without induction of ventricular fibrillation. The rabbits in group B as an epinephrine group were administered with 30 g/kg epinephrineduring CPR. The rabbits in group C as a MNE group were administered with 100 g/kg a-MNE during CPR. The left ventricular end-diastolic pressure (LVEDP), left ventricular pressure rise and fall rate (±dp/dt) and serum concentrations of BNP were measured. Statistical package of SPSS 10.0 was used for data analysis and significant differences between means were evaluated by ANOVA. RESULTS:Compared to group A, the LVEDP of other two groups increased respectively (P<0.01 all), and peak±dp/dt decreased in the other two groups (P<0.01). The increase of LVEDP was lower in group C than in group B (P<0.05), whereas peak±dp/dt was higher in group C than in group B (P<0.05) at the same stage. Compared to group A, the cTnT of the remaining two groups increased, respectively (P<0.01), and peaked at 30 minutes. cTnT was less elevated in group C than in group B (P<0.05) during the same period. In groups B and C, myocardial injury was seen under a light microscope, but the injury in group C was lighter than that in group B. CONCLUSION:Methylnorepinephrine can lessen myocardial dysfunction after CPR.

BACKGROUND:Sepsis has become the greatest threat to in-patients, with a mortality of over 25％.The dysfunction of gut barrier, especially the immunological barrier, plays an important role in the development of sepsis. This dysfunction occurs after surgery, but the magnitude of change does not differentiate patients with sepsis from those without sepsis. Increased intestinal permeability before surgery is of no value in predicating sepsis. The present study aimed to observe the changes of intestinal mucosal immunologic barrier in rat models of sepsis induced by cecal ligation and puncture. METHODS:Sixty Sprague-Dawley rats were randomly divided into a sepsis group (n=45) and a control group (n=15). The rats in the sepsis group were subjected to cecal ligation and puncture (CLP), whereas the rats in the control group underwent a sham operation. The ileac mucosa and segments were harvested 3, 6 and 12 hours after CLP, and blood samples were collected. Pathological changes, protein levels of defensin-5 (RD-5) and trefoil factor-3 (TFF3) mRNA, and lymphocytes apoptosis in the intestinal mucosa were determined. In an additional experiment, the gut-origin bacterial DNA in blood was detected. RESULTS:The intestinal mucosa showed marked injury with loss of ileal villi, desquamation of epithelium, detachment of lamina propria, hemorrhage and ulceration in the sepsis group. The expression of TFF3 mRNA and level of RD-5 protein were decreased and the apoptosis of mucosal lymphocyte increased (P<0.05) in the sepsis group compared with the control group. Significant differences were observed in RD-5 and TFF3 mRNA 3 hours after CLP and they were progressively increased 6 and 12 hours after CLP in the sepsis group compared with the control group (P<0.05, RD-5 F=11.76, TFF3 F=16.86 and apoptosis F=122.52). In addition, the gut-origin bacterial DNA detected in plasma was positive in the sepsis group. CONCLUSION:The immunological function of the intestinal mucosa was impaired in septic rats and further deteriorated in the course of sepsis.