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.

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 bufalin on proliferation and expression of WT1 in K562 cells. Methods The colony number of K562 cell was detec-ted with semi-solid culture assay. The cell cycle was measured by flowcytometry, and the expression of WT1 was observed with immunocytochemistry. Subcutaneous tumor models established by K562 cells in BALB/C nu/nu mice were divided into three groups, including model group, bufalin group and positive control group. After 21 days, the subcutaneous tumors were removed for calculating the inhibitory rate of tumor growth. HE staining and immunohistochemistry were used to ob-serve the morphological changes and the expression of WT1 . Results ① Bufalin could significantly decrease the colony number of K562 cell, arrest it at G0/G1 phase and down-regulate its expression of WT1 in a dose-dependent manner. ② Compared with the model group, the tumor inhibitory rate was much higher, while the volume and the weight were obviously lower in the other two groups. ③Bufalin could induce apop-tosis, necrosis, hemorrhage and fibrosis with HE stai-ning, and down-regulate the expression of WT1. Con-clusion Bufalin could inhibit the proliferation, arrest the cell cycle at G0/G1 phase and down-regulate the expression of WT1 in vitro. Bufalin could inhibit the tumor inhibitory rate, the volume and the weight of the subcutaneous tumors, induce apoptosis, necrosis, hemorrhage and fibrosis with HE staining and down-regulate the expression of WT1 .

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.

To investigate the curative effect of individualized treatment on peripheral facial paralysis. Methods:A treatment group of 121 patients was treated with acupuncture under an individualized plan based on the condition of disease. For a control study,118 patients were treated with conventional acupuncture. The courses of treatment and the curative effects were compared. Results:The cure and marked efficacy rate was 90.9% in the treatment group and 69.5% in the control group. There was a significant difference (P＜0.01).There was also a significant difference in the cure and marked efficacy rate in each courses of treatment between the two groups (P＜0.01). Conclusion:Individualized acupuncture treatment is better in the effect and shorter in the courses than conventional acupuncture treatment for peripheral facial paralysis.

Objective To explore the regional reference intervals of biomarkers in umbilical blood for diagnosis of early onset bacterial infection in the healthy term newborns .Methods The umbilical blood samples were collected from 1 476 term newborns in our hospital during January 2012 to October 2013 ,of which 1 191 were healthy infants and enrolled in this study .Then the levels of high sensitive c‐reaction protein(hs‐CRP) ,procalcitonin(PCT) ,interleukin(IL)‐6 ,IL‐8 ,platelet(PLT) as well as white blood cell (WBC) were detected in the umbilical blood .These values were analyzed by SAS 9 .0 ,data were described through upper or lower limits or upper limits respectively .Differences among different subgroups were judged through analysis of Kruskal‐Wallis t test or Mann‐Whitney test respectively .Results The upper limits for hs‐CRP was 3 .1 mg/L ,for PCT was 0 .18 ng/mL ,while the refer‐ence interval for IL‐6 was 56 .6(11 .9-133 .2)ng/L ,and IL 8 was 976 .0(111 .7-2 507 .1)ng/L ,PLT was 242 .0(120 .0-339 .0)× 109/L and for WBC was 12 .9(7 .6-19 .3 )× 10 9/L ,and the value of PLT varied from vaginal delivery group to caesarean section group(230 vs .254 ,Z= 4 .301 ,P< 0 .05);no significant differences were found in these biomarkers among different gestational week specific groups (P>0 .05) .Otherwise ,compared with the regional reference intervals ,CRP and PCT in early onset neonatal sepsis group increased(P<0 .05) ,no significant difference was found for IL‐6 ,IL‐8 ,WBC and PLT (P>0 .05) .Conclusion The reference intervals of biomarkers in umbilical blood for diagnosis of early onset bacterial infection were established which may make great contribution for early diagnosis of bacterial infection for the newborns .