The receptor-interacting protein (RIP) has been identified to play a critical role in necroptosis, which is an inflammatory form of programmed necrosis in trauma, ischemia/reperfusion (I/R), and systemic inflammatory response syndrome (SIRS). Ripoptosome, a newly defined intracellular signaling complex with essential molecule of RIP1, can switch cell death mode between apoptosis and necroptosis. Based on molecular mechanism of RIP-dependent cell death and inflammation, with the understanding of the mechanisms of RIP-dependent apoptosis/necroptosis and its role in inflammation was summed up, and it was found that RIP plays a crucial role in regulating programmed cell death and inflammation. Therefore, further advances in understanding the mechanisms of necroptosis would be important in order to manipulate programmed cell death for therapeutic purposes in I/R injury, trauma, SIRS, and tumor.

Objective To investigate the value of pro-adrenomedullin (pro-ADM) levels for severity as-sessment of community-acquired pneumonia (CAP).Methods 214 CAP patients who were admitted to the emer-gency department were prospectively studied.The levels of plasma pro-ADM were determined using a new sandwich immunoassay.At the same time, procalcitonin, C-reactive protein, interleukin-6 levels, leukocyte count, clinical varia-bles and the pneumonia severity index (PSI) were measured.Results Pro-ADM levels,in contrast to procalcitonin,interleukin-6 levels, increased with increasing of the severity of CAP, which was classified according to the PSI score (P<0.05).In patients who died during follow-up, pro-ADM levels on admission were significantly higher than that in survivors [2.08 vs.4.94 μg/L,Z=-4.081 ,P<0.001].In a receiver operating characteristic (ROC) analysis for survival, the area under the ROC curve (AUC) for pro-ADM was 0.79, which was significantly higher than that for procalcitonin(0.72), C-reactive protein (0.58), interleukin-6 (0.64 ), and total leukocyte count (0.50) and sim-ilar to the AUC of the PSI (0.75).Conclusion Pro-ADM is a useful biomarker for the risk stratification of CAP patients.

The neurotoxin peptide, hainantoxin-Ⅵ (HNTX- Ⅵ), has been isolated from the venom of Chinese tarantula Ornithoconus hainana by a combination of ion exchange chromatography and reverse phase HPLC. The toxin was found to contain 34 amino acid residues with 6 conserved cysteine residues. The effects of HNTX-VI on voltage-gated sodium channels were studied via whole-cell patch clamp techniques. Although several inhibitors of mammalian neuronal sodium channel activation (hainantoxin Ⅰ-Ⅴ) had been characterized from the same venom, the present study indicated that HNTX-Ⅵ had the ability to slow the inactivation kinetics of the sodium channels in Cockroach Periplaneta Americana dorsal unpaired median (DUM) neurons in a similar manner to δ-atractoxins. After HNTX-Ⅵ treatment, steady-state sodium channel inactivation became incomplete, leading to a non-inactivating component at potentials more positive than - 55 mV. The novel function of the tarantula toxin HNTX-Ⅵ not only supplies a useful tool for exploring the gating mechanisms of sodium channels but also provides theoretical foundations for exploiting novel and safe insecticides.

Objective To observe the levels of HIF-α and TGF-β in the liver tissue,change of serum transaminase in different phases after paraquat (PQ) toxicity and liver histopathology change in PQinduced liver toxicity of rats models in order to analyze the relationship between HIF-1 α and hepatic toxicity induced by PQ.Methods A total of 48 healthy SD rats were randomly (random number) assigned into 2 groups:PQ poisoning group (n =42,20％ PQ solution,50 mg/kg in 1mL) and control group (n =6,normal saline 1mL).Rats were separately sacrificed and liver tissue samples were harvested at 2,6,12,24,48,72 h and 120 h after PQ administered by gastric lavage.Arterial blood gas (ABG) analysis and serum alanine transaminase were assayed.Liver tissue HE and Masson staining and immunochemistry changes were also investigated.HIF-1α and TGF-β levels were detected by Western blot technique.Results Lactic acid level was significantly higher in PQ group than that in control group at 6 h after PQ exposure (P ＜ 0.05).The level of serum alanine transaminase was increased and significantly higher if PQ group than that in control group at 2 h after PQ poisoning (P ＜ 0.05).The level of HIF-1 α and TGF-β protein in the liver tissue were up-regulated significantly and higher in PQ group than those in control group at 2 h after PQ exposure (P ＜ 0.05).The hepatocytes necrosis and inflammatory cells infiltration were observed around portal area 2 h after PQ poisoning.At 12 h after PQ exposure,the periportal area filled with necrosis of hepatocytes and the necrosis began to extend,and huge amounts of inflammatory cell infiltration were found.Cord-like fibroplasia was found.All the histological changes were around central portal area and were enlarged gradually.Conclusions The results show that there are increased level of HIF-1 α in the early stage of PQ poisoning rats.The liver fibroplasia may be associated with increasing the level of TGF-β promoted by HIF-1α.

Objective To investigate the related risk factors,clinical features and prognosis of hospital-acquired acute kidney injury (AKI) in intensive care unit (ICU).Methods We retrospectively analyzed 48 patients with both acute kidney injury and multiple organ dysfunction syndrome (MODS),who received renal replacement therapy from October 2006 to February 2011 in our ICU.According to whether the occurrence time of AKI was 48 hours after admission,they were divided into hospital-acquired AKI (HA-AKI) group and community-acquired AKI (CA-AKI) group,with 13 and 35 cases respectively.We compared the differences between these two groups in gender,age,acute physiology and chronic health evaluation Ⅲ (APACHE Ⅲ),primary diseases,days of mechanical ventilation,times of renal replacement therapy,number and indicators of organ failure,prognosis,renal function recovery,length of stay in ICU and hospital.Results The mean age of HA-AKI group is ( 64.5 ± 21.4) years,which is older than that in CA-AKI group ( 50.2 ± 17.5 ) years (P=0.022).The top three primary diseases in CA-AKI group are severe infection(42.8％ ),chronic kidney disease (CKD) concurrency of AKI ( 11.4％ ) and multiple trauma without head injury ( 8.6％ ).However severe infection still occupies the first in HA-AKI group ( 30.8％ ),followed by stroke (23.1％,P=0.024),multiple trauma with head injury( 15.4％,P=0.018 ) and gastrointestinal bleeding( 15.4％ ) ;Patients in HA-AKI group with more than four organ failures account for 84.6％,significantly higher than 65.7％ in CA-AKI group (P=0.000).On the first day,the levels of serum sodium ( P =0.036 ) and bicarbonate ( P=0.001 ) in HA-AKI group are higher than that in CA-AKI group,and the urinary volume is more(P =0.046).In HA-AKI group,the level of urea nitrogen on the seven day increases so progressively that it becomes significantly higher than that on the first day(P=0.015),but in CA-AKI group,there is no significant change in the levels of serum creatinine and urea nitrogen after AKI,while the levels of seruum sodium ( P=0.023 ) and bicarbonate ( P=0.030) increase significantly;APACHE Ⅲ score in HA-AKI group after admission 24 hours is significandy lower than that in CA-AKI group(53.2 ±22.8) point vs (89.1±25.7) point,P=0.000),and the length of stay in ICU and hospital and days of mechanical ventilation in HA-AKI group are significantly longer than that in CA-AKI group,but there are no significant differences in times of RRT therapy,prognosis and recovery of renal function.Conclusion APACHE Ⅲ score after 24 hours of admission does not accurately reflect the prognosis of patients with MODS and HA-AKI.There are great differences in age,primary diseases,organ function changes and other aspects of HA-AKI when compared with CA-AKI.

Objective To explore the effective evaluation methods of case-based learning (CBL) in critical disease teaching.Methods Totally 53 undergraduate students in department of clinical medicine of Shanghai Jiao Tong University,who practiced in our hospital from 2010 to 2012,were divided into the traditional teaching group and CBL teaching group.We used traditional teaching combining with CBL teaching in CBL group.Common cases of critical illness(severe acute pancreatitis and multiple trauma)in intensive care unit (ICU) were selected for CBL cases.The evaluation of theoretical knowledge,mini-clinical evaluation exercise(Mini-CEX)and direct observation of procedural skills (DOPS) were continued after teaching and practice.Results These was no significant difference in the theoretical knowledge examination between the two groups. In Mini-CEX,the students in CBL group were better concerning the medical interview capacity (P=0.000),humanistic care (P=0.013),clinical diagnosis(P=0.035),counseling(P=0.009) and the overall clinical competence (P=0.008) than those in traditional teaching group.The DOPS scores of endotracheal intubation (P=0.016)and central venous catheterization (P=0.001)discussed in CBL teaching were significantly higher in CBL group.Conclusion Traditional theoretical knowledge examination has little significance in the assessment of CBL teaching,but Mini-CEX and DOPS can reflect the advantages of CBL teaching better in the assessment of clinical abilities and skills.

ObjectiveTo study the HIF-1α expression in rats with paraquat poisoning (PQP).MethodsNinety-six healthy SD rats were randomly (random number) divided into 2 groups ( n =48 in each group) : PQP group and control group. The PQP group was further divided into six subgroups as per thedifferent intervals after Paraquat intoxication. Samples from 6 PQP subgroups and control group were taken at 0 h, and 2 h, 6 h, 12 h, 24 h, 48 h, 72 h and 120 h after paraquat administration. Aarterial blood wascollected for blood gas analysis, and the sections of lung tissue were stained with hematoxyhn-eosin and masson's trichrome to detect the trichrome positive area, and HIF-1α was detected by immunohistochemistryAll data were processed with one-factor analysis of variance and Pearson correlation analysis. ResultsTwo hours after paraquat poisoning, the levels of HIF-1α protein and the collagen were both significantly upregulated in the lung tissue in rats with paraquat poisoning. However, the hypoxemia existed until 72h.There was correlation between levels of Masson's trichrome positive area and HIF-1α positive area (r =0. 819, P ＜0. 05 ). There was correlation between the levels of lactic acid in blood gas analysis and HIF-1α positive area (r=0. 761, P＜0. 05. But there was no correlation between levels ofPO2 and HIF-1α positive area (r=-5.24, P＞0. 05). ConclusionsThe level of HIF-1α was up-regulated in rats with paraquat poisoning and it was not associated with hypoxemla.

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.

Objective To evaluate the effect on inflammatory mediators and mechanism of dynamic factors on lung injury in a dog model of acute respiratory distress syndrome (ARDS). Method The ARDS dog model was duplicated by instillation hydrochloric acid. The dogs were randomly (random number) divided into six groups: (1) normal control group (N group); (2) ARDS group (M group); (3) low VT (6 mL/kg) at respiratory rate 30, low inspiratory flow 6 mL/(kg·s). (4) large VT (20 mL/kg) at respiratory rate 30, high inspiratory flow 20 mL/kg·s.(5) large VT (20 mL/kg) at respiratory rate 15, high inspiratory flow 17 mL/(kg·s). (6) large VT (20 mL/kg) at respiratory rate 15, low inspiratory flow 10 mL/(kg·s). All the dogs were killed after 4 h ventilation. TNF-α、IL-8, p38 MAPK and NF-κB activity in the lung were measured. Results The expression of IL-8 protein in B and C groups was much higher than that of other groups ( P < 0.01) . There was no significant difference among M, A and D groups (P > 0.05). The gray scale ratio of B group was obviously higher than that of other groups (P < 0.01), except C group (P > 0.05). There was no significant changes among M, A and D groups in TNF-α protein contents. p38 MAPK value of positive staining of B group was the strongest, significantlyhigher than that of D group ( P < 0.01) .The expression of p38 MAPK in B and C groups was much higher than other groups (P <0.01). NF-κB activity in B group (33.56±2.85%) was significantly higher than that in A (10.35±0.6%)、D(7. 11 ± 0.47%)group, but there was no difference between B and C group (30.87 ± 1.16%). Conclusions Ventilation at high tidal volume, high inspiratory flow rate, high respiratory rate could activate p38 MAPK and increase the activity of NF-κB with the result of aggravating the release of inflammatory mediators. p38 MAPK and NF-κB activation are the major mechanisms in the development of VILI.

Aim To investigate the effect of resveratrol on proliferation and differentiation in K562 cells. Methods K562 cells were treated with different con-centrations of resveratrol for 6d. The colony number of K562 cells was detected with semi-solid culture assay. Expression of GATA-1 and PU. 1 in K562 cells was re-spectively measured with immunocytochemistry and Western blot. Expression of differentiation related anti-gen, CD11b, CD14 and CD42b, was measured with flowcytometry on K562 cells. Results Resveratrol
could significantly decrease the colony number of K562 cells in a dose-dependent manner, and enhance the ex-pression of GATA-1,PU. 1,CD11b, CD14 and CD42b in K562 cells. Conclusion Resveratrol could inhibit the proliferation and induce differentiation of K562 cells via up-regulating the expression of GATA-1 and PU. 1 protein.