Research progress on the common pathogenesis of Parkinson′s disease and rapid eye movement sleep behavior disorder / 中华神经科杂志

Parkinson′s disease (PD) is one of the neurodegenerative diseases with high incidence in middle-aged and elderly people, and its prodromal stage lasts for several years to decades, markers of disease progression in prodromal stage are important basis for early recognition and diagnosis of PD. Current studies have shown that rapid eye movement sleep behavior disorder (RBD) is the specific clinical prodromal symptoms of PD, and has some of the same mechanisms as PD. Part of the same mechanisms develop regularly in the process of RBD converting to PD, which may produce valuable prodromal markers of PD. This paper reviews the common mechanisms of PD and RBD, in order to provide some ideas for the early clinical diagnosis and treatment of PD.

Effects of chitinase-3-like protein 1 on the expression of inflammatory damage-related molecules in mouse skeletal muscle satellite cells induced by lipopolysaccharide / 中华危重病急救医学

Objective:To explore the potential mechanism of chitinase-3-like protein 1 (CHI3L1) involved in skeletal muscle stem cell injury induced by sepsis.Methods:Six different concentrations of lipopolysaccharide (LPS) were used to stimulate mouse skeletal muscle satellite cells cultured in vitro. Enzyme linked immunosorbent assay (ELISA) and cell counting kit-8 (CCK-8) were used to determine the optimal concentration. The overexpression and interference vectors of CHI3L1 were constructed to transfect skeletal muscle satellite cells, and the transfection efficiency was verified by polymerase chain reaction (PCR) and Western blotting. The cells were randomly divided into blank control group (cells without any intervention), model group (LPS-stimulated untransfected cells), overexpressing CHI3L1 group (LPS-stimulated cells transfected with CHI3L1 plasmid), overexpressing CHI3L1 control group [LPS-stimulated cells transfected with negative control (NC) plasmid], CHI3L1 interference group [LPS-stimulated cells transfected with CHI3L1 small interfering RNA (siRNA)], CHI3L1 interference control group (LPS-stimulated cells transfected with CHI3L1-siRNA NC). The levels of extracellular caspase-1 and interleukin-1β (IL-1β) were detected by ELISA. The protein expressions of intracellular IL-1β, signal transducer and activator of transcription 3 (STAT3), protein kinase B (Akt) and phosphorylated Akt (p-Akt) were detected by Western blotting. Results:According to the results of CCK-8 and ELISA, the best concentration of 5 mg/L LPS was selected for the subsequent experiment. The transfection was validated by PCR and Western blotting. Compared with the blank control group, the levels of extracellular IL-1β, caspase-1 and the protein expressions of intracellular Akt, p-Akt, and IL-1β were significantly increased in the model group [IL-1β (ng/L): 11.22±0.55 vs. 8.63±0.63, caspase-1 (pmol/L): 9.47±0.22 vs. 8.65±0.15, Akt/GAPDH: 1.36±0.12 vs. 1.06±0.15, p-Akt/GAPDH: 0.78±0.07 vs. 0.09±0.01, IL-1β/GAPDH: 1.38±0.12 vs. 0.18±0.03, all P < 0.05]. Compared with the model group and the overexpressing CHI3L1 control group, the levels of extracellular IL-1β, caspase-1 and the protein expressions of intracellular p-Akt and IL-1β were significantly increased in the overexpressing CHI3L1 group [IL-1β(ng/L): 14.93±0.97 vs. 11.22±0.55, 9.38±0.40, caspase-1 (pmol/L): 10.35±0.03 vs. 9.47±0.22, 8.46±0.24, p-Akt/GAPDH: 1.21±0.04 vs. 0.78±0.07, 0.63±0.04, IL-1β/GAPDH: 1.87±0.08 vs. 1.38±0.12, 1.51±0.17, all P < 0.05]. Compared with the model group and the CHI3L1 interference control group, the levels of extracellular IL-1β, caspase-1 and the protein expressions of intracellular p-Akt and IL-1β were significantly decreased in the CHI3L1 interference group [IL-1β(ng/L): 8.98±0.73 vs. 11.22±0.55, 10.44±0.65, caspase-1 (pmol/L): 7.61±0.63 vs. 9.47±0.22, 8.37±0.38, p-Akt/GAPDH: 0.50±0.04 vs. 0.78±0.07, 0.94±0.06, IL-1β/GAPDH: 0.77±0.02 vs. 1.38±0.12, 1.13±0.07, all P < 0.05]. Conclusions:CHI3L1 may mediate the damage of skeletal muscle stem cells in sepsis by increasing the expression of caspase-1 and IL-1β. CHI3L1 may be involved in the regulation of Akt signaling pathway in skeletal muscle stem cells, but has no significant effect on STAT3 signaling pathway.

Update in immune regulatory dysfunction of dendritic cells in sepsis / 中华烧伤杂志

Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection. Further development of sepsis usually leads to septic shock or even death. Many previous studies have focused on the abnormal reactions of monocytes/macrophages, neutrophils, complement system, or cytokine inflammation in sepsis. Many evidences in recent years suggest that dendritic cells, as the most powerful antigen-presenting cells in innate immune system of body, play important role during the process of immune disorders of sepsis. In this article, I review the main classification, immune function, monitoring method, regulatory pathways of dendritic cells and their clinical significance in immune disorders of sepsis, so as to find new strategies for immune regulation of sepsis.

Update in immune regulatory pathway of tumor necrosis factor-α-induced protein 8-like 2 / 中华危重病急救医学

The tumor necrosis factor-α-induced protein 8-like (TNFAIP8, TIPE) family is recently identified proteins consisting of four highly homologous mammalian proteins: TIPE, TIPE1, TIPE2, and TIPE3. Although the four members share similar molecular structure and function, involving effects in pathophysiological processes of inflammation, immunity, tumors, stroke, angiogenesis, and other diseases, they have individual characteristics. Many studies have shown that TIPE2 is an essential negative regulator of both innate and adaptive immunity. Up-regulation of TIPE2 expression can alleviate excessive inflammation during septic shock and maintain hemostasis of macrophages, neutrophils, dendritic cells, T cells, and B cells. In this review, we summarize the current literature for structure feature, immune function, and regulatory mechanism of TIPE2, together with its clinical significance in the pathogenesis of immune disorders of a wide array of human diseases. Understanding the basic biology of this new molecule might help us to seek novel strategies for the immunomodulation of human diseases.

Prognostic significance of plasma gelsolin in severe burn patients with sepsis / 中华烧伤杂志

<p><b>OBJECTIVE</b>To investigate the changes in plasma gelsolin (pGSN) levels in severe burn patients with sepsis, and to evaluate the prognosis of patients when combined with other related clinical indexes.</p><p><b>METHODS</b>Sixty-five severe burn patients with sepsis hospitalized from June 2013 to June 2015 conforming to the study criteria were divided into death group (n=24) and survival group (n=41) according to the clinical outcome on post sepsis diagnosis day (PSD) 28. The pGSN levels of patients were determined on PSD 1, 3, 7, and 14 with double antibody sandwich enzyme-linked immunosorbent assay. The serum level of C-reactive protein (CRP), serum level of procalcitonin, lactate level of arterial blood, Acute Physiology and Chronic Health Evaluation (APACHE) II score, and Sequential Organ Failure Assessment (SOFA) score were determined or recorded on PSD 1. Data were processed with repeated measurement analysis of variance, t test, and chi-square test. On PSD 1, the pGSN level, serum level of CRP, serum level of procalcitonin, lactate level of arterial blood, APACHE II score, and SOFA score of 65 patients were collected to screen the independent risk factors related to death with single factor and multi-factor Logistic regression analysis. Receiver operating characteristic (ROC) curves of the independent risk factors related to death were plotted to evaluate the predictive power for death in 65 patients.</p><p><b>RESULTS</b>(1) The pGSN levels of patients in death group on PSD 1, 3, 7, and 14 were respectively (146±44), (85±24), (28±7), and (19±4) mg/L, obviously lower than those in survival group [(287±82), (179±51), (196±56), and (249±67) mg/L, with t values from 1.735 to 4.304, P<0.05 or P<0.01]. (2) The serum level of CRP, serum level of procalcitonin, lactate level of arterial blood, APACHE II score, and SOFA score of patients in death group on PSD 1 were respectively (56±7) mg/L, (12.54±0.82) μg/L, (2.74±0.27) mmol/L, (24.3±2.4) points, and (11.43±0.57) points, significantly higher than those in survival group [(35±4) mg/L, (2.38±0.16) μg/L, (1.83±0.12) mmol/L, (15.0±1.5) points, and (7.22±0.23) points, with t values from 1.902 to 3.883, P<0.05 or P<0.01]. (3) Multi-factor Logistic regression analysis showed that the pGSN level (odds ratio: 6.83, 95% confidence interval: 4.33-10.25, P<0.01) and APACHE II score (odds ratio: 5.27, 95% confidence interval: 2.28-9.16, P<0.01) were the independent risk factors related to death in 65 patients on PSD 1. (4) The total areas under the ROC curves of pGSN level and APACHE II score for predicting death of 65 patients on PSD 1 were respectively 0.89 and 0.86, and 142 mg/L and 21 points were respectively chosen as the optimal threshold values, with sensitivity of 87% and 83% and specificity of 86% and 89%.</p><p><b>CONCLUSIONS</b>For severe burn patients with sepsis, lowering of pGSN level and elevation of APACHE II score are obviously correlated with increase in case fatality rates. Monitoring the dynamic changes in pGSN level and APACHE II score during the early stage may be useful to predict the prognosis of severe burn patients with sepsis.</p>

The effects of sodium pyruvate Ringer solution on hemodynamic and organ functions during shock stage in dogs with a 50％ total body surface area full-thickness burn / 中华危重病急救医学

Objective To compare the effect of intravenous resuscitation with sodium pyruvate (Pyr) Ringer solution against lactated Ringer solution on hemodynamic and organ functions during shock stage in dogs with burn.Methods 28 Beagle dogs were subjected to 50％ total body surface area (TBSA) burn,and they were divided into three groups:burn injury without fluid resuscitation (N R,n =8),Ringer lactate solution(RL,n =10),and Pyr Ringer solution (RP,n =10).They were given intravenous fluid resuscitation according to Parkland formula 30 minutes after burn.The hemodynamics,organ functions and mortality were observed in conscious state before burn injury,and 2,6,8,12,24 hours after burn injury.Results Within 24 hours after burn,all the dogs in NR group died,and those in RL and RP groups were all alive.At 2 hours after burn,the mean arterial pressure (MAP),cardiac index (CI),dp/dt max of left ventricular contractility were significantly reduced in NR,RL and RP groups compared with those before injury [MAP(mmHg,1 mmHg =0.133 kPa):45.33 ± 7.78 vs.141.67 ± 5.98,91.33 ± 10.25 vs.142.33 ± 6.16,98.67 ± 9.54 vs.142.83 ±5.47; CI (mL·s-1·m-2):8.17 ±0.83 vs.48.34 ±3.33,16.84 ±2.17 vs.47.34 ± 1.67,19.00 ± 1.50 vs.47.34 ± 1.33; dp/dt max (mmHg/s):426.83 ± 51.91 vs.1 372.50 ± 39.61,594.00 ± 88.23 vs.1 363.83 ± 44.92,645.00 ±66.82 vs.1 395.83 ± 19.49,all P＜0.05],and the systemic vascular resistance (SVR) and alanine transaminase (ALT),creatinine (Cr),serum MB isoenzyme of creatine kinase (CK-MB),diamine oxidase (DAO) were significantly higher [SVR (kPa·s ·L-1):1 322.50 ±36.37 vs.281.45 ± 8.84,777.50 ±41.84 vs.289.72 ± 6.70,571.40 ±40.01 vs.286.27 ±8.66; ALT (U/L):89.50 ±4.11 vs.40.57 ±3.63,89.25 ±4.88 vs.37.92 ± 2.62,86.30 ±5.61 vs.38.47 ±3.50; Cr (μmol/L):75.62 ±4.61 vs.41.58 ±2.78,77.00 ±5.92 vs.46.55 ± 3.17,74.13 ±2.56 vs.45.65 ± 1.83; CK-MB (kU/L):13.122 ±0.282 vs.1.557 ±0.009,8.885 ±0.272 vs.1.497 ± 0.009,8.692 ± 0.180 vs.1.490 ± 0.005; DAO (kU/L):2.26 ± 0.14 vs.0.25 ± 0.02,1.50 ± 0.07 vs.0.25 ± 0.01,1.37 ± 0.07 vs.0.25 ± 0.02,all P＜0.05].All parameters in NR group kept on worsening till death,while hemodynamic and organ functions of two intravenous resuscitation groups were gradually improved,CI,SVR and DAO in RP group were significantly superior to those of RL group from 2 hours on after burn (all P＜0.05),and dp/dt max and CK-MB in RP group were significantly better than those of RL group from 6 hours on after burn [dp/dt max (mmHg/s):1 082.33 ± 63.59 vs.1 018.60 ± 47.36,CK-MB (U/L):7 898.70 ± 255.74 vs.8 438.70 ± 442.00,all P＜0.05],and MAP (mmHg) was significantly better than that of RL group at 6 hours (124.67 ± 9.39 vs.114.33 ± 9.16,P＜0.05),and Cr (tμmol/L) was significantly better than that of RL group from 24 hours on after burn (53.42 ± 4.99 vs.60.77 ± 3.11,P＜0.05).Conclusion The Pyr Ringer solution was superior to the Ringer lactate solution in improving hemodynamic and organ functions for intravenous resuscitation in dogs with 50％TBSA full thickness burn.

Effect of Pyruvate-enriched ORS on intestinal mucosal blood flow, activity of Na+-K+-ATPase and intesti-nal absorption rate during enteral resuscitation of scalded rats / 医学研究生学报

Objective Gastrointestinal rehydration is a simple and effective method in treatment of burn shock during war-time, fire disaster and other harsh conditions , and practice has proved the exact curative effect of HCO 3 salt sugar liquid .This article was to investigate the effect of pyruvate-enriched oral rehydration solution ( Pyr-ORS ) on intestinal mucosal blood flow ( IMBF ) , activity of Na +-K+-ATPase and intestinal absorption rate during en-teral resuscitation of a 35% TBSA third-degree scald in rats . Methods 90 male rats were randomly divided into 5 groups: scald without fluid resuscitation ( S group ); sham scald resuscitated with HCO3 salt sugar liquid ( SS HCO3 group ); sham scald resuscitated with Pyr-ORS ( SS Pyr-ORS group ); scald resuscitated with HCO 3 salt sugar liquid (S HCO3 group); scald resuscitated with Pyr-ORS (S Pyr-ORS group) (n=18).Each group was divided into 2 subgroups of 1.5 and 4.5 h after scald injury.Intestinal absorption rate of water and Na +, IMBF and activity of Na +-K+-ATPase were detected on each group . Results Compared with shame scald groups , the intestinal absorption rates of water and Na +decreased ob-viously in scald groups with fluid resuscitation (P<0.05);at 1 h after scald injury, the intestinal absorption rates of water and Na +in S Pyr-ORS groups were both higher than those in S HCO 3 groups(P<0.05).Compared with shame scald groups , IMBF and activity of Na+-K+-ATPase at 1.5 and 4.5 h after scald injury decreased obviously in scald groups with fluid resuscitation (P<0.05); at 1.5 and 4.5 h after scald injury, IMBF in S Pyr-ORS groups (95.250 ±5.096/112.765 ±7.215) were greater than those in S HCO3 group (80.764 ±7.852/94.671 ±8.469), which was of statistical significance (P<0.05). Conclusion Pyr-ORS is a simple and effec-tive method in treatment of burn shock during wartime , fire disaster and other harsh conditions .

Antagonistic effect of astragaloside on immune response of regulatory T cells mediated by high mobility group box-1 protein in rats / 中华创伤杂志

Objective To investigate the antagonistic effect of different doses of astragaloside Ⅳ (AST Ⅳ) on immune function of regulatory T (Treg) cells mediated by high mobility group box-1 protein (HMGB1) in rats and the mechanism by which AST Ⅳ exerts its influence.Methods CD4 + CD25 +Treg cells isolated from the spleens of clean-grade BALB/c mice were seeded on 72-well culture plate.Cells were divided into four groups (18 wells per group) according to the random number table,i.e.normal control group (cells were cultured merely),HMGB1 (1 μg/ml) group,HMGB1 (1 μg/ml) + AST Ⅳ (50 μg/ml) group,and HMGB1 (1 μg/ml)+AST Ⅳ (100 μg/ml) group.Each group consisted of three subgroups (6 wells per group),from which the Treg cells were collected at post-stimulation hours 24,48 and 72 respectively.Foxp3 intracellular protein and mRAN expressions were detected by flow cytometry and quantitative fluorescent PCR.Contents of IL-10 and TGF-β released into the supernatants were determined by ELISA method.Results As compared with the control group,Foxp3 intracellular protein and mRAN expressions in the Treg cells were decreased at 24 hours to 72 hours after HMGB1 stimulation (P ＜ 0.01),with particular reduction at 72 hours.Additionally,changes of IL-10 and TGF-βin the supernatants presented the same trends with Foxp3.Foxp3 protein and mRAN expressions in AST Ⅳ group were markedly higher than that in HMGB1 group at 24-72 hours (P ＜ 0.05) and the expressions in AST Ⅳ(100 μg/ml) group were much more significant than that in AST Ⅳ (50 μg/ml) group (P ＜ 0.05).While contents of IL-10 and TGF-β in supernatants revealed the same trend with Fox3 as well.Conclusions AST Ⅳ antagonizes the impact of HMGB1 on the activity of the Treg cells in a dose-dependent manner in vitro.It is suggested that AST Ⅳ has a strong inhibitory effect on HMGB1-mediated inflammatory response.

Effects of oral rehydration on tissue perfusion, organ function and survival rate in rats with 40% blood volume loss hemorrhagic shock / 中华创伤杂志

Objective To investigate the effects of oral glucose-electrolyte solution (GES) on resuscitation of hemorrhagic shock induced by 40% blood volume loss in rats. Methods SD rats were randomly divided into three groups; oral GES without hemorrhagic shock (GES group, n = 16) , hemorrhage shock without fluid resuscitation (HS group, n = 20) and hemorrhagic shock resuscitated with oral GES (HS + GES group, n = 20). About 40% of total blood volume was bled from carotid artery of rats to produce a model of hemorrhagic shock. GES with a volume of three times of blood loss was given three times intragastrically at 0.5, 1 and 6 hours after hemorrhage. Mean arterial pressure (MAP) was measured constantly. Blood flow in liver, kidney, stomach and small intestines, and parameters like hemato-crit, plasma osmotic pressure, alanine aminotransferase (ALT) , creatinine (Cr) and diamine oxidase (DAO) were determined 24 hours after hemorrhage. Survival rates of the rats in three groups were calculated 24 hours after hemorrhage. Results MAPs of HS + GES group were 9. 7% and 10. 9% higher than those of HS group 4 and 24 hours after hemorrhage (P < 0. 05). The blood flow of liver, stomach and small intestines in HS + GES group were 18.6% , 88.4% and 22.0% respectively, higher than those in HS group(P <0.05 or P <0.01) 24 hours after hemorrhage. The hematocrit level of HS + GES group was significantly lower than that of HS group, while the levels of ALT, Cr and DAO in HS + GES group were significantly lower than those in HS group (P <0.01). The survival rate of rats in HS + GES group was 80% , which was significantly higher than 30% in HS group (P <0.01). Conclusions Oral rehydration can significantly improve MAP and tissue perfusion, maintain blood volume and plasma osmotic pressure, alleviate organ damage and hence promote the survival rates of rats with hemorrhagic shock.

Efficacy of neoadjuvant regional arterial chemotherapy for patients with advanced gastric cancer / 中华消化外科杂志

Objective To investigate the efficacy and toxicity of neoadjuvant regional arterial chemotherapy in the treatment of advanced gastric cancer. Methods The clinical data of 158 patients with advanced gastric cancer and with the same clinical stages who were admitted to Renji Hospital of Shanghai Jiaotong University from February 2002 to May 2005 were retrospectively analysed. Preoperative regional arterial chemotherapy was applied to 76 patients (test group) and the remaining 82 patients only received surgical treatment (control group). The chemotherapy regimen was epirubicin (50 mg/m2) + cisplatin (60 mg/m2) + 5-fluorouracil (1000 mg/m2).This regimen was modified to oxaliplatin (130 mg/m2) + 5-fluorouracil (1000 mg/m2) since 2003, and surgery was performed 6-11 days after the chemotherapy. All patients received postoperative intravenous chemotherapy.The clinical effects, radical resection rate, operative complications and long-term survival of the two treatment methods were evaluated. All data were analysed using the chi-square test and Kaplan-Meier analysis. Results The radical resection rate was significantly higher at 86% (65/76) in the test group compared with 71% (58/82)in the control group ( x2 = 5.01, P ＜ 0. 05 ). The toxicity of the chemotherapy in the test group was mild. The postoperative complication rate was 20% (15/76) in the test group and 16% (13/82) in the control group, with no significant difference between the two groups (x2 = 0.41, P＞0.05). The median survival time was 41 months in the test group and 23 months in the control group. The 5-year overall survival rate was higher in the test group (44.6%) than that in the control group (29.1%) (x2 =3.95, P＜0. 05). Conclusions Neoadjuvant regional arterial chemotherapy is well tolerated by patients with advanced gastric cancer. It is also effective for increasing the radical resection rate and improving the long-term survival.

Immunological activity change of regulatory T cells and its relation with outcome of patients with severe burn / 中华创伤杂志

Objective To investigate the immunological activity change of regulatory T cells (Treg) and discuss its significance in the outcomes of patients with multiple organ dysfunction syndrome (MODS) and severe burn. Methods A total of 106 patients with total burn surface area (TBSA) larger than 30% were included in the study and randomly divided into three groups according to the burn area: Group Ⅰ (TBSA of 30%-49%, n = 41), Group Ⅱ (TBSA of 50% -69%, n = 34) and Group Ⅲ (TBSA of 70%-99%, n = 31). According to the development of MODS, patients were divided into MODS group (n =21) and non-MODS group (n =85). The patients with MODS were further divided into non-survival group (n = 16) and survival group (n = 5) based on their outcomes. Healthy volunteers were served as normal control (n = 25). Peripheral blood samples were collected at days 1,3,7, 14 and 21 postburn. The immunomagnetic separation technique was applied to separate and purify CD4+ CD25+Tregs in peripheral blood, and phenotypes (CTLA-4) were analyzed by flow cytometry and the contents of interleukin-10 released in the supernatants were determined by ELISA. Results Expression of CTLA-4 and level of IL-10 were significantly increased in burn patients compared with normal control group, with statistical differences. The expression of CTLA-4 and level of IL-10 were significantly increased in patients with severe burns at all time points. The expression of CTLA-4 and level of IL-10 in MODS group were much higher than those in non-MODS group at days 3-21 postburn (P ＜ 0.01). Among the MODS patients, the expression of CTLA-4 and level of IL-10 in the survival group were obviously lower than those in the non-survival group at days 3-21 postburn (P ＜ 0.05 or P ＜ 0.01). Conclusions After severe burn injury, expressions of the markers on CD4 + CD25 + Treg surface and secretion of cytokines produced by CD4 + CD25 + Tregs show significant difference in patients with different born areas, MODS development and survival state. CD4 + CD25 + Treg may play an important role in the pathogenesis of immunoregulation, MODS and mortality of burn patients through secretion of inhibitory cytokines.

Development of animal model of early oral fluid resuscitation of burn shock / 中华创伤杂志

Objective To establish an animal model for study on early oral fluid resuscitation of burn shock so as to provide experimental basis for oral fluid resuscitation of burn shock in wars, accidents or disasters. Methods Male Beagle dogs weighing 11-13 kg were used in the study and the carotis, jugular and duodenum were cannulated respectively for measurement of homodynamics, tissue perfusion and gastrointestinal function. Dogs were subjected to a 35% TBSA full thickness flame injury with 10-mi-nute anesthesia by intravenous injection of propofol 24 hours later, and then randomly and equally divided into two groups(8 dogs in each group) : no fluid resuscitation group (NR group) undergoing no treatment in the first 24 hours post burn and oral fluid resuscitation group ( OR group) undergoing gastric infusion of glucose electrolyte solution (GES) according to Parkland formula. From the second 24 hours post burn, animals in two groups were given delayed Ⅳ fluid resuscitation, and then intravenous nutritional support was initiated at the 72nd hour. The mean arterial pressures (MAP), cardiac output (CO), dp/dt max of left ventricular contractility (dp/dtmax) and plasma volume (PV) were monitored continuously. The pa-rameters of gastrointestinal tissue peffusion, the rates of gastric emptying and intestinal absorption of GES were determined, the morbidity was also recorded at the end of 5-day experiment. Results After 35% TBSA burn injury, MAP, CO,dp/dt max and PV dropped markedly and gastrointestinal tissue perfusion reduced obviously. CO and PV in OR group were significantly higher than those in NG group at 4, 8 and 24 hours after burn. Homodynamic parameters and gastrointestinal tissue perfusion in OR group were pro-moted to pre-injury level at 48 and 72 hours respectively, while homodynamic parameters in NR group did not return to pre-injury level till 72 hours, and gastrointestinal tissue perfusion kept lower than pre-injury till 120 hours post burn. Rates of gastric emptying and intestinal absorption of GES significantly reduced to the lowest level (42% and 37% of pre-injury) at about 4 hours post bum, but did not return to pre-in-jury level till eight hours post bum. Over five days, two out of eight dogs (25%) died in NG group but none in OR group. Conclusions The animal model can exactly simulate the actual circumstance, where oral resuscitation is superior to Ⅳ resuscitation in some aspects in treating early bum shock in wars, accidents and disasters, and provide practical and reliable method for measurement of homodynamic parameters, tissue perfusion, gastric emptying and intestinal absorptive function.

Effects of oral fluid resuscitation on circulatory oxygen dynamic parameters in dogs with burn shock / 中华急诊医学杂志

Objective To investigate the effect of oral fluid resuscitation on circulatory oxygen dynamic parameters in dogs with burn shock.Method Eighteen male Beagle dogs were surgically prepared for the cannulation of carotid cartery and jugular vein,subjected to flame injury 50%total body surface area(TBSA)with fullthick ness 24 hours later,and they then randomly divided into 3 equal groups.The oral fluid resuscitation group (OR group)was intragastrieally injected with infusion of glucose-electrolyte solution(GES)according to parkland formula 0.5h after burn with a dose of 4mL·kg-1·% TBSA-1.Intravenous (IV) GES resuscitation group (VR group)was intravenously injected with infusion of GES as the same dose as OR group,and no-fluid resuscitation (NR)group did not receive any treatment during the first 24 hotrs.In the second 24 hours,all dogs received Ⅳ fluid resuscitation.At the end of 72 hours of injury.the mortality in each group was recorded.The mean arterial arterial pressure(MAP),hematocrit(HCT)and blood lactic acid(LAC)were determined,and blood gas analysis was evaluated for oxygen delivery(DO2),oxygen consumption(VO2)and oxygen uptake(O2ext)before injury and 2,4,8,24,48 and 72 hours after injury.Results Burn injury resulted in a 77.1%decrease in MAP,and a 48.5% increase in HCT and 533.7%increase in LAC in NR group,followed by pngressively lowering of DO2,VO2 and Oext till all animals died with in 24 hours after burn.MAP and HCT levels oftwo resuscitation groups gradually returned to the pre-injury levels within 72 hours after burn,but the LAC levels sill remained significantly higher than the pte-injury levels(P＜0.01).The MAPs of OR group were higher at corresponding intervals within 24 hours post burn than those of NR group(P＜0.01),but they were lower than those of VR group(P＜0.01).The serum LAC in OR group was markedly lowered than that in NR group,but it was higher than that in VR group.Twenty-four hours after burn injury,the DO2 level in OR group showed no significant differences compared with that of the VR group,but the levels of the VO2 and Oext were still much lower than those of VR group (P＜0.01).At the end of 72 hours,3 dogs of NR group died and none of IV group died.Caadusions Oral fluid resuscitation improves oxygen dynamic,alleviates hyperlactacidemia and reduces the mortality of animals with severe burn shock.

Effect of carbachol on the expression of la on monocyte and lymphocyte apoptosis rate of the burned rats with delayed resuscitation / 中国医师杂志

Objective To explore the changing trend of Ia on monocyte, lymphocyte apoptosis rate, TNF-α and IL-6 in abdominal aorta of burned rats with delayed resuscitation and the influence of application of carbachol on them. Methods Adult male Wistar rats were randomly divided into normal control group(n =8), scald group(n =48) and scald with carbachol treatment group(n =48). In latter two groups, rats were inflicted with 30% total body surface area (TBSA) full-thickness scald and delayed fluid resuscitation. All scald rats were sacrificed at the 6th hours or 1st, 2nd, 3rd, 7th, 14th day after scald, with 8 rats at each time point. Expression of Ia antigen on monocyte and lymphocyte apoptosis rate were determined by direct immunofluorescence on a flow cytometer, and TNF-α and IL-6 was measured by ELISA. Results Expression of la on monocyte was obviously lower than that of controls. The lowest levels were recorded on the 6th hours and 1st day after scald. Subsequently, Ia was elevated gradually, but still lower than that of normal rats(P <0. 01). After administration of carbachol, Ia expression was obviously promoted, compared with the simple scald group (P <0. 01). Lymphocyte apoptosis rate, TNF-α and IL-6 was higher than that of controls(P <0. 01). After administration of cavachol, , lymphocyte apoptosis rate and TNF-α and IL-6 was obviously down-regulated on the 6th hours, 1st day, 2nd day and 3rd day after scald injury, compared with the simple scald group (P < 0. 01 or 0. 05). Conclusion After severe burn with delayed fluid resuscitation, there is a low la expression, high lymphocyte apoptosis rate and increased releasing of proinflammatory cytokine. Immune function was suppressed. Carbacho] could improve the immune function of scald rats with delayed fluid resuscitation.

Functional study of p38 mitogen-activated protein kinase based on cell-penetrating peptide delivery system / 老年心脏病学杂志（英文版）

Objective p38 Mitogen-activated protein kinase (MAPK) is a crossing center of various pathways. In this study, protein transduction system based on human immunodeficiency virus (HIV)-1 transactivator of transcription (TAT), which is an efficient delivery peptide of the foreign proteins into cells, was employed to study p38 MAPK functions in eukaryotic cells. Methods p38 And its dominant negative form, p38AF, were constructed into pET-His-TAT vector correctly to verify that the recombinant plasmids were well-founded through restriction enzyme digestion and DNA sequencing. The two proteins, His-TAT-p38 and His-TAT-p38AF, were expressed and purified in Escherichia coli by SDS-PAGE. Then they were incubated with ECV304 cells respectively and readily transduced into cells in a time-dependent and dose-dependent manner. The cells were stimulated by sorbitol. Activating transcription factor (ATF) 2 phosphorylation level was checked using Western blot to assess the activity of endogenous p38. Results Compared with controls, it was found that His-TAT-p38 increased the level ofATF2 phosphorylation in sorbitol-stimulated ECV304 cells, while His-TAT-p38AF inhibited it, indicating p38 MAPK protein delivery system based on TAT was constructed successfully. TAT-p38 and its dominant negative form possessed high biological activity after transduction into ECV304 cells by TAT protein delivery system. The results showed that p38AF fused with TAT could inhibit the transduction of endogenous p38 signal pathway in part, and other pathway might regulate p38 phosphorylation. Conclusions Our study provides a novel pathway to inhibit p38 signal pathway and establish a new method to study p38 function.

Dysfunction of neuroendocrine system in sepsis and implication of hormone therapy / 老年心脏病学杂志（英文版）

Abstract Sepsis and related syndromes are the major cause of multiple organ failure and death in patients with critical illnesses.Neuroendocrine dysfunction has long been thought to be an important event in sepsis.In clinic,optimal management of the hormones could alleviate severe complications in sepsis.In this article,we review the dysfunction of neuroendocrine system as well as autonomic nervous system in sepsis,and summarize the respective therapy strategies.

Carbachol alleviates intestinal inflammation during enteral fluid resuscitation of rats with burn shock / 中华急诊医学杂志

Objective To investigate the effect of carbachol on local gut inflammation during entetal resuscitation of rats with bum shock. Method Thirty-eight Wistar rats were subjected to 35%TBSA full thickness scald injury, and enteral fluid was infused into animal intestines via duodenal stomas 30 minutes post bum. The animals were randomly divided into four groups: no resuscitation (Control, n = 8), enteral resuscitation using either a glucose electrolyte solution (GES, n = 10) or GES plus carbachol (60 μg·kg-1,GES/CAR, n = 10), or carbachol alone (CAR, n = 10) .The volumeof GES infusion was based on the Parkland formula (4 ml· 1% TB-SA-1·Kg-1) - All animals were sacrificed 4 hours post bum, and specimens of jejunal tissue were collected to determine the levels of tumor necrosis factor (TNF)-α, nitric oxide (NO), nitric oxide synthase (NOS) and myeloperoxidase (MPO). Serum assays for plasma diamine oxidase (DAO) activities were also performed. Results There were no statistical differences in the intestinal levels of NOS, NO, TNF-α and MPO, and plasma OAO activities, between the GES group and the control group. Compared to the GES group, the GES/CAR group showed significantly lowered levels of intestinal NOS (1.276 ±0.391 vs. 1.818 ±0.436, P＜0.05), NO (0.925 ±0.402 vs. 1.561 ±0.190, P ＜ 0.05, TNF-α (0.87±0.13 vs. 1.94±0.47, P ＜0.01) and MPO (0.465 ±0.092 vs. 0.832±0.214, P＜0.05),and reduction in plasma DAO activites (0.732±0.192 vs. 1.381 ±0.564, P ＜0.05). The CAR group also showed significantly lowered levels of intestinal NOS, NO, TNF-α and MPO and reduced plasma DAO activites, compared to the GES group. Conclusions Theses results suggest that carbachol significantly inhibits the release of proinflammatory mediator and attenuates local inflammation in gut during enteral fluid resuscitation of rats in rats with bum shock. We postulate that carbachol may exert its and-inflammatory effects via the cholinergic anti-inflammatory pathway.

Effects of dynamic ventilatory factors on extrapulmonary inflammatory response and function of extrapulmonary organs in a dog model of acute respiratory distress syndrome / 中华急诊医学杂志

Objective To investigate the effects of dynamic ventilatory factors on inflammatory response and function of extrapulmonary organs in acute respiratory distress syndrome (ARDS) dogs. Method Thirty-six healthy dogs were randomly divided into 6 groups: normal control group (N group), ARDS group ( M group) and ventilation groups (A～D groups)hased on a series of random number. The ARDS dog model was replicated by iutrawacheal instillation of hydrochloric acid and mechanical ventilation was carried out according to the following protocols. Group A:low VT, low inspiratory flow and high respiratory rate. Group B: large VT, high inspiratory flow and high respiratory rate. Group C: large VT, high inspiratory flow and low respiratory rate. Group D: large VT, low inspiratory flow and low respiratory rate. After 4 hours of mechanical ventilation, animals were sacrificed.Tumor necrosis factor (TNF)-α and intefleukin (IL)-8 levels in blood serum were measured by radioimmunoassay.Histopathological changes of liver and kidney were observed under light microscope. Results The level of IL-8 and TNF-u of group B and C were much higher than those of group D, A and M ( P<0.05), but there was no significant difference among group D, A and M ( P>0.05). The level of IL-8 and TNF-α of group N were much lower than other groups ( P<0.05). The change of histopathology was the most significant in group B and C while the change of histopathology on group C was better than group B. The change of histopathology on group A and D was better than group B and C. The change of group A was similar to group M. All the data were analyzed by statistical F test. There was statistical difference with P<0.05. Comclusions Large tidal volumes with high inspiratory flow and high respiratory rate may increase mediators of inflammation in blood sennn, and aggravate the irflamnnmtory response of extrapulmonary organs. Beducfion of inspiratory flow and respiratory rate ventilation may prevent the occurrence d multiple organ dysfunction syndrome.

Effect of rapamycin(RPM)on interleukin-10 gene expression in rats with postburn Staphylococcus aureus sepsis / 中华急诊医学杂志

Objective To investigate the effect of rapamycin(RPM)on hepatic interleukin-10(IL-10)gene and acute liver injury in rats with postburn Staphylococcus aureus sepsis.Methods Fifty male Wistar rats were randomly divided into four groups:normal control group,scald control group,postburn sepsis group,and RPM treatment group.Tissue samples from liver and plasma were collected to determine IL-10 mRNA and protein expressions,and liver function parameters were also measured.Results Compared to postburn Staphylococcus aureus sepsis group,in RPM treatment group hepatic IL-10 mRNA expression and plasma IL-10 were significantly increased at 0.5 hour after RPM treatment(P

Coordinated Regulation of MAPK and STAT3 Proteins on TNF-? Transcription Activity / 生物化学与生物物理进展

In order to investigate if there exists interaction between mitogen-activated protein kinase (MAPK) and signal transducer and activator of transcription 3 (STAT3) protein, and how the interaction regulates tumor necrosis factor-? (TNF-?) transcription activity, the human p38 and extracellular-signal regulated protein kinase 2 (ERK2) genes were amplified from human flag-p38 and flag-ERK2 by polymerase chain reaction (PCR) and cloned into pcDNA3-HA. Protein expression of the plasmids was examined by Western blotting. Co-immunoprecipitation was used to identify if there exists interaction between MAPK and STAT3 proteins. If the interaction was approved to be true, report gene system was applied to find how the interaction affect transcriptional expression of TNF-?. After STAT3 pathway was inhibited by RNA interfering, the action on TNF-? activity was determined. The results of DNA sequencing and enzyme digestion showed that the cloned p38 and ERK2 genes were correct, to be 1 080 bp or so. p38 and ERK2 proteins were expressed in 293T cell to be approximately 40 ku. Co-immunoprecipitation data showed that p38 and ERK2 proteins integrated with STAT3 protein in vivo. TNF-? reporter gene activity results found that protein complex of p38-STAT3 and ERK2-STAT3 coordinately increased TNF-? activity. After STAT3 was interfered, the TNF-? activity markedly decreased. These data indicated that there exists interaction between p38 and STAT3 protein, ERK2 and STAT3 protein. The complex of the proteins can coordinately regulate TNF-? expression. After interfereing STAT3 pathway, the coordinated action on TNF-? transcription activity might be obviously reduced.