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A multicenter confirmatory study about practicability and precision of the third edition of SepsisObjective:To evaluate the adherence to the guidelines in six hospital system in china,with emphasis on the practicability and precision of new and old edition of Sepsis definition.Methods:This observational study was implemented in intensive care unit in six hospital in southeast of china over 6-month period starting on 1 January and ending on 31 June 2015,retrospectively collected data on patients aged 18 years or older who met criteria for the second edition of Sepsis or the third edition of Sepsis,and then divided to different group according the distinct hospital,to investigated the diagnosis rate in different degree hospital.To estimate the independent effect of each factors and dignosis,univariate unadjusted logistic regression were used in two group which separated by diagnosis.in other two group(A group represented patients who was diagnosis as Sepsis according to Sepsis 3.0,B group included people was Sepsis in Sepsis 2.0 but not in Sepsis 3.0),the characteristic of patients was compared.Receiver operating characteristic curve(ROC)was performed to evaluate the systemic inflammatory response syndrome(SIRS),the quick Sequential[Sepsis-related]Organ Failure Assessment(QSOFA)and the Sequential[Sepsis-related]Organ Failure Assessment(SOFA),and whether the consistency of QSOFA and SOFA would affect the sensitivity of definition.Lastly,univariate unadjusted logistic regression was performed in death group and survivor group to investigate those factors associate with death.Result:1423 patients admitted to ICU were screened,Of 363,329 subjects who met Sepsis 2.0 and Sepsis 3.0 respectively.no significant differences were found between the group of Sepsis 2.0 and the group of Sepsis 3.0 except Apache II score(P<0.05),in partial,center 3 which has the lowest rate of diagnosis with the highest mortality(60.4%).In contrast to center 1,they has the lowest mortality of Sepsis,but they also did not recognized Sepsis frequently as we excepted(19.5%).Interestingly,center 4has the highest diagnosis rate of Sepsis but mortality was 58.6%.univariate logistic regression was performed with a view to find those factors infected diagnosis,results showed diagnosis was negatively correlated with age,lactate level and blood pressure,and positive correlation to PaO2/FiO2.Compared to B group,patients seems to be younger[year:53.75(18.00)VS 68.52(26.00)],had lower apache2 score[score:7.72(6.00)VS 20.38(8.00)],level of lactate[mmol/L:1.95(1.20)VS 3.45(3.00)],less people die from Sepsis[13.90(5)VS 45.29(149)],and shorter length of ICU stay[d:15.13(16.00)VS 22.42(22.00)]in group A.The Area Under the ROC Curve of SIRS,QSOFA and SOFA is 0.57,0.60,0.68 separately,indicated that prognostic value to mortality was increased,but it still had space to improve.We divide patients into groups according to fulfill QSOFA or(and)SOFA,and the result indicated that significant different was exist between the two group in term of APACHE II score and mortality,even the patients who met the QSOFA,their mortality was up to 38.8%,suggested that we should not ignore QSOFA.Logistic regression shown that there were only APACHE II score(P=0.00)and length of ICU stay(P=0.00)effect on death.Conclusion patients of Sepsis 3.0 trend to be have more organ failure issues,the specificity of Sepsis 3.0 was higher than Sepsis 2.0,but data suggested that the still long way to go to improve the definition.Part ? Protective effect and mechanism of simvastatin in different dosage form on co-culture of Endothelial Cells and Smooth Muscle Cells under sepsis conditionObjective:This research mainly explores the protective effects and the possible molecular mechanisms of simvastatin on EC and SMC were induced by LPS.And the improvement of the drug dosage form,nanoparticles,is aslo our goal.Methods:By given LPS,sepsis pattern was induced in ECs and SMCs,meanwhile cells were theated with simvastatin nanoparticles and common vein dosage form,the rate of apoptosis was analyzed by flow cytometer.The changes of the expression of AKT and eNOS in ECs was detected by western bolt.The concentration of IL-6 in ECs and SMCs cell medium were detect by ELISA method.The siRNA test and trans well experiments detect SMCs and ECs migration ability both in coculture model and alone culture.Quantitative Polymerase Chain Reaction and Western blot to detecting how ECs mediate SMCs durning this pathophysiologic process of sepsis.Results:(1)After given LPS,simvastatin can inhibited the increasing rate of apoptosis induce by LPS,simvastatin can activated the PI3K/AKT pathway to promote the expression of eNOS.(2)LPS can increase the secretion of IL-6 in SMCs,also can promote the production of TNF-ain ECs.Simvastatin decreased the IL-6 obviously in SMC and the TNF-a in EC.And in coculture group,like EC,compared to single culture group the secretion of IL-6 was decreased dramatically,regarding to SMCs,only LPS group decrease signifidently when compared to single coculture group.(3)In term of migration,the result of trans well indicated that simvastatin can change the expression of IQGAP1 protein to infect the migration of SMCs,accordingly it can influence the secretion of PDGF in ECs which can effect on the migration of SMCs too.Conclusions:(1)Simvastatin can blunted EC cell apoptosis to maintaining the normal function of the vascular epithelium,simvastatin can activated the PI3K/AKT pathway to promote the expression of eNOS.It is important to maintain the balance of iNOS/eNOS in sepsis.(2)Simvastatin can inhibit the IL-6 release in SMC and the TNF-a secretion in EC.(3)Simvastatin can inhibit SMCs and ECs migration to maintaining the normal function of the vascular epithelium.(4)Nanoparticles as a new type of medicine preparations.The effect is superior to other agents in some of our experiment. |
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