Sepsis,life-threatening organ dysfunction caused by a dysregulated host response to infection,is a major public health concern.To date,the mechanism of sepsis is not completely understood,which is still a huge task ahead of numerous clinical and laboratory researchers.Recently,increasing evidences show that deacetylase sirtuins play an important role in sepsis and the function of sirtuins are varied in different stages of sepsis.More importantly,the mechanism of sirutins is not fully understood.The sirtuins family is composed by sirtuin 1-7 members.Among them,sirtuin 1 is widely reported.In addition to sirtuin 1,other members of sirtuins are also involved in the regulation of inflammation or metabolism signaling following sepsis.Of note,the sirtuins may interact with each other and form a precious control mechanism.Herein,we tried to summarize the recent paper from PubMed,to explain the possible mechanism of distinct role of sirtuin 1/2,to generalize the downstream effects of sirtuin 3 action,and to describe the interactions among sirtuins members on sepsis,which might be helpful for our future research and potential clinical applications.

Objective To investigate relationship between the variation degree of platelet mitochondria in rats with severe hemorrhagic shock and the degree of shock.Methods Thirty-six Wistar rats were divided into sham group,shock 30,60,and 120 minutes groups,shock 120 minutes + normal saline (NS) + blood reinfusion group (NS group) and shock 120 minutes + polydatin (PD) + blood reinfusion group (PD group) according to random number table,with six rats per group.Content of ATP in platelets was detected by fluorescein-luciferase assay kit; structure of platelet mitochondria by electron microscope; state of mitochondrial permeability transition pore by Calcein-AM and CoCl2 ; change of mitochondrial membrane potential (△Ψm) by JC-1 mitochondrial membrane potential kit; lipid hydroperoxide (LPO) in platelets by LPO assay kit; stability of platelet lysosomes by acridine orange (AO).Results ATP released from platelets was reduced significantly in shock 60 minutes group (P ＜0.01) and with the prolong of shock period,further reduction was observed,particularly in NS group [(50.75 ± 9.15)％ of normal value].Mitochondrial swelling with poorly defined crista structure,declined △Ψ and low lysosome stability (pale cells were increased) were observed in shock 30 minutes group.Calcein fluorescence in mitochondria was faded in shock 60 minutes group (P ＜ 0.01).Whereas in PD group,all the above indices presented some recovery with ATP level returned to nearly (79.57 ± 8.48) ％ of normal value in particular.Conclusions Platelet mitochondrial dysfunction takes place at 30-60 minutes following severe shock.Hence,it may be served as an non-invasive index for the diagnose and treatment of severe shock.

BACKGROUND:Basic fibroblast growth factor(bFGF)can promote production of collagen,fibronectin and matrix enzyme in healing wounds.However,dysregulation of this process,such as the abnormal coordination of cell proliferation,extracellular.matrix and neovasculadzation formation,or remodeling of the wound matrix will lead to excess accumulation of scar tissues.OBJECTIVE:To investigate effects of bFGF on normal skin wound healing and hypertrophic scar formation.METHODS:Normal and hypertrophic scar fibroblasts from tissue biopsies from 5 patients who underwent plastic surgery for repairing hypertrophic scars were isolated and cultured.The expressions of collagen,fibronectin and protein synthesis were detected by RT-PCR and ELISA.The mitochonddal membrane potential changes were measured using JC-1 staining and flow cytometry.Simultaneously,adenosine tdphosphate(ATP)levels were determined by chemiluminescence method.The effects of bFGF on these indexes of normal and hypertrophic scar fibroblasts were observed.RESULTS AND CONCLUSION:Hypertrophic scar fibroblasts become slower after being exposed to bFGF,which selectively inhibited type Ⅰ collagen production in hypertrophic scar fibroblasts(P<0.05).Although bFGF inhibited type]collagen production,it had no effect on type Ⅲ collagen expression in both normal and hypertrophic scar fibroblasts.However,fibronectin expression in the normal fibroblasts was up-reguleted after bFGF treatment(P<0.05).In addition,the mitochonddal membrane potential tended to depolarization,although no statistical difference,in hypertrophic scar fibroblasts treated with bFGF(10 or 100 μg/L).bFGF treatment increased the cellular ATP levels in the normal fibroblasts,while there were no significant alterations in the hypertrophic scar fibroblasts over a treatment of bFGF(10 or 100 μg/L,P<0.05).The results suggest that there are differential effects and mechanisms on the skin fibroblasts with bFGF treatment in normal wound healing and hypertrophic scar formation.

Objective:To investigate the feasibility and safety of a new method of natural orifice transluminal endoscopic surgery(NOTES) -totally transtracheal endoscopic thyroidectomy(TTET) .Methods:Three miniature swines and 6 beagle dogs were underwent TTET.Under general anesthesia,special designed endotracheal tube with 2-channel was used and endoscope and instruments were inserted through the respective channel.Incision of tracheal anterior wall was accomplished and partial or subtotal thyroidectomy was performed.Finally,the defects in the trachea were sutured with ENDO STITCH instrument.Results:Partial thyroidectomy was successfully accomplished on 3 pigs and subtotal thyroidectomy was done on 6 dogs.No serious complications such as anoxia,asphyxia,airway obstruction and death occurred during the operation.Animals were sacrificed 2h after the procedure and incision of trachea was found to be closely sutured.There were no subcutaneous emphysema and haematoma formation.Conclusion:Preliminary experimental results showed the feasibility and safety of TTET.Transtracheal access maintains the integrity of cervical tissues and achieves an optimal cosmetic outcome.TTET may open up a new field of NOTES on thyroid surgery.

Objective To determine the effects of two fluid resuscitation strategies on the changes of hemodynamic variables,serum concentration of tumor necrosis factor-alpha(TNF-α)and interleukin-6 (IL-6)in a clinically relevant model of uncontrolled hemorrhagic shock in pregnant rabbits.Methods Hemorrhagic shock was induced by bleeding via carotied artery,followed by transection of a medium vessel in gestational sac.Experimental design consisted of three phases,shock phase(0-30 min),prehospital phase(30-90 min)and hospital phase(90-180 min).Twenty pregnant rabbits were randomly divided into two groups(n=10/group),aggressive fluid resuscitation group(PNL group)and limited volume resuscitation group(PLH group).In the shock phase,animals were hemorrhaged by blood withdrawal to mean arterial pressure(MAP)of 40-45 mm Hg(1 mm Hg=0.133 kPa)via carotid artery.In the prehospital phase,a medium vessel in the gestational sac was transected,then the animals in the PNL group and PLH group were resuscitated with 0.9% normal saline(NS)and shed blood to MAP of 80,60 mm Hg respectively.In the hospital phase,bleeding was controlled by surgical intervention and all the animals were reinfused with shed blood and NS to MAP 80 mm Hg.Hemodvnamic variables and respiration rate were monitored and blood samples were collected for TNF-α and IL-6 measurement.and finally subsequent volume resuscitation and survival rate were recorded.Results (1)At 120 min,the respiration rate and heart rate in the animals assigned to PLH group was(66±16)bpm,(235±41)bpm respectively,which were significantly lower than those in PNL group(P＜0.01),while MAP and central venous pressure in the PLH group was(80.4±7.2)mm Hg,(8.0±4.4)cm H2O,respectively,which were significantly higher than those in PNL group(P＜0.01);(2)The serum concentration of TNF-α,IL-6 of all the animals were markedly increased after hemorrhagic shock.and peak at 24 min.The serum concentration of TNF-α,IL-6 in animals assigned to PLH group were(105±67)ng/L,(118±51)ng/L respectively,which were significantly lower than those in PNL group(P＜0.01).The serum concentration of TNF-α,IL-6 in the animals assigned to PLH group were decreased to normal at 480 min;(3)The subsequent blood transfusion volume and NS resuscitation volume in PLH group in prehospital phase were(16.0±2.2)ml,(39.0±5.5)ml respectively,while those in hospital phase were(28.0±6.7)ml,(90.0±7.1)ml respectively,which were significantly lower than those in PNL group(P＜0.05);(4)The 24 and 72 hours survival rate in the animals assigned to PLH group were 100%,90% respectively;which were significantly higher than those in PNL group(P＜0.01).Conclusion Limited volume resuscitation improves thermodynamic changes of pregnant rabbit,attenuates the increase of serum concentration of TNF-α,IL-6,and results in higher survival rate.Limited volume resuscitation is an ideal means for hemorrhagic shock resuscitation in pregnant rabbit.

Objective To elucidate the role of P38 signaling pathway on heat-induced apoptosis in monocytic cell line Raw264.7.Methods Raw cells were transfected with constitutively active mutant MKK6b(E)and dominant negative mutant P38(AF),or the empty cloning vector pcDNA3 and apoptosis was detected by flow cytometric analysis.Results The ectopic expression of P38 mutant was confirmed by immunostaining with the antibody against the Flag-epitope tag.Expression of MKK6b(E)led to a marked increase in P38 kinase activity in transfected cells and induced a 4-fold increase in the number of apoptotic cells as compared to that in cultures of control transfected cells.Meanwhile the expression of MKK6b(E)increased the apoptotic rate of Raw cells induced by heat.In contrast,the dominant-negative mutant P38(AF)inhibited Raw cells apoptosis induced by heat.Conclusion The activation of the MKK6-P38 MAP kinase signaling pathway is required for heat-induced apoptosis in Raw264.7 cells.

AIM: To study the effect of microelement powder (MP) on membrane potential of vascular endothelial and smooth muscle cells of rats in order to elucidate the mechanism of microcirculation improvement by MP. METHODS: Cultured pulmonary vascular endothelial cells (EC) and aortic smooth muscle cells (SMC) of rats and detecting the changes of cellular membrane potentials by using potential-sensitive fluorescent probe and laser jet confocal microscope. RESULTS: MP hyperpolarized SMCs significantly. Glybenclamide (2 μmol/L), a blocker of KATP channel, which had no effect on membrane potential of SMCs, reversed the hyperpolarization of MP completely; MP hyperpolarized ECs slightly, but the effect was unaffected by glybenclamide. CONCLUSION: MP hyperpolarizes SMCs by activating KATP channels and leads to dilation of microvessels and improvement of microcirculation.

OBJECTIVE: To elucidate the mechanism of vascular hyporeactivity following severe hemorrhagic shock (HS) by studying the changes of ATP-sensitive potassium channels' (K(ATP)) properties and membrane potential of mesenteric arteriolar smooth muscle cells. METHODS: Single channel currents were studied on cell-attached and inside-out patches of enzymatically isolated mesenteric arteriolar smooth muscle cells (ASMCs). Membrane potentials of arteriolar strips and ASMCs were recorded by intracellular membrane potential recording method and confocal microscopy, respectively. RESULTS: K(ATP) channels in ASMCs were activated, which induced smooth muscle hyperpolarization following vascular hyporeactivity in HS. CONCLUSIONS: Hyperpolarizing effect of K(ATP) channel activation plays an important role in low vasoreactivity during severe hemorrhagic shock.

AIM: To investigate the variation of nitric oxide(NO) and NO synthase(NOS) in rats during the early stage of severe burn and their possible relation with prognosis of severe burns.METHODS: Levels of NO - 2/NO - 3, the metabolic products of NO, nNOS and iNOS protein in brain, lung and duodenum of rats were measured before and after burns. Survival times of rats in each group were also measured.RESULTS: Levels of NO - 2/NO - 3 in rats after burn increased remarkably, selective inducible NOS( iNOS) inhibitor aminoguanidine (AG), and nonselective NOS inhibitor L-NAME can inhibit this increasing. Levels of neuronal NOS(nNOS) protein in normal rats were low, and iNOS could not be detected. Levels of nNOS protein increased mildly in all observed tissues and the levels of iNOS protein increased remarkably after burn. Administration of L-NAME and AG made the increase of nNOS more apparently but could not affect the level of iNOS. Survival time of rats decreased in L-NAME group and increased in AG group compared to control group.CONCLUSION: Symptoms such as vascular ralaxation and hypotension in burn shock are connected mainly with over-increased iNOS. [

AIM: To investigate whether small GTPase RhoA's downstream effector Rho kinase mediates burn serum-induced endothelial hyperpermeability. METHODS: Primary cultured rat dermal microvascular endothelial cells (DMECs) were exposed to serum isolated from burned or sham burn rats for 6 hours and 8 hours, respectively, and did or didn't pretreated or post-treated with Y-27632 (30 ?mol/L), a specific inhibitor of Rho kinase. ECs were then prepared for routine scanning electron microscopy observation, or stained with rhodamine-phalloidin for F-actin visualization. Permeability to FITC-albumin was evaluated using EC monolayers. RESULTS: Stimulation with 15% burn serum for 6 h changed the ultrastructure on cellular surface of DMECs with appearance of ripple marks instead of microvillus. The small protuberances at cellular lateral were shorten and the gaps were seen between adjacent cells. Post-treatment of Y-27632 reversed the changes of ultrastructure on the cellular surface. Burn serum induced a striking reorganization of actin cytoskeleton with a weakening of fluorescent intensity of the peripheral filament bands and formation of the long and thick stress fibers, lamellipodia and filopodia. The stress fibers were diminished by pretreatment or post-treatment of Y-27632. But lamellipodia and filopodia were not influenced by pretreatment or post-treatment of Y-27632. Pre-treatment of Y-27632 also attenuated significantly the increase in EC monolayer permeability stimulated by burn serum for 6 h. However, post-treatment of Y-27632 could not attenuated burn serum-induced endothelial hyperpermeability response although their Pa values were lower than simple burn serum group's. CONCLUSION: These findings indicate that Rho kinase is involved in the mediation of burn serum-induced endothelial actin cytoskeleton reorganization and early stage of barrier dysfunction. [