Minimum quality threshold in preclinical sepsis studies (MQTiPSS): quality threshold for fluid resuscitation and antimicrobial therapy endpoints / 中华危重病急救医学

As outlined in the International Guidelines for Management of Sepsis and Septic Shock: 2016, initial fluid resuscitation and administration of antibiotics are key steps in the early management of sepsis and septic shock. However, such clear guidelines do not exist for preclinical sepsis models. To address these shortcomings, the Wiggers-Bernard conference on preclinical sepsis models was held in Vienna in May 2017. The participants reviewed 260 of the most highly cited papers between 2003 and 2012 that used sepsis models. The review demonstrated that over 70% of experiments either did not use or failed to report resuscitation and/or antibiotic treatment. This information served as the basis to create a series of recommendations and considerations for preclinical sepsis models; this Part Ⅲ report details the recommendations for fluid resuscitation and antibiotic treatment that should be addressed in sepsis models. Similar to human sepsis, fluid resuscitation is recommended in the experimental setting unless part of the study. Iso-osmolar crystalloid solutions are preferred. The administration route and its timing should be adjusted to the specific requirements of the model with preference given to dynamic rather than static hemodynamic monitoring. Predefined endpoints for fluid resuscitation and avoidance of fluid overload should be considered. Preclinical sepsis studies display serious inconsistencies in the use of antimicrobial protocols. To remedy this, antimicrobials are recommended for preclinical studies, with choice and dose adjusted to the specific sepsis model and pathogen(s). Ideally, the administration of antimicrobials should closely mimic clinical practice, taking into account the drug's pharmacokinetic profile, alterations in absorption, distribution and clearance, and host factors such as age, weight, and comorbidities. These recommendations and considerations are proposed as "best practices" for animal models of sepsis that should be implemented.

Minimum quality threshold in pre-clinical sepsis studies (MQTiPSS): quality thresholds for study design and humane modeling endpoints / 中华危重病急救医学

Preclinical animal studies are mandatory before new treatments can be tested in clinical trials. However, their use in developing new therapies for sepsis has been controversial because of limitations of the models and inconsistencies with the clinical conditions. In consideration of the revised definition for clinical sepsis and septic shock (Sepsis-3), a Wiggers-Bernard Conference was held in Vienna in May 2017 to propose standardized guidelines on preclinical sepsis modeling. The participants conducted a literature review of 260 most highly cited scientific articles on sepsis models published between 2003 and 2012. The review showed, for example, that mice were used in 79% and euthanasia criteria were defined in 9% of the studies. PartⅠof this report details the recommendations for study design and humane modeling endpoints that should be addressed in sepsis models. The first recommendation is that survival follow-up should reflect the clinical time course of the infectious agent used in the sepsis model. Furthermore, it is recommended that therapeutic interventions should be initiated after the septic insult replicating clinical care. To define an unbiased and reproducible association between a new treatment and outcome, a randomization and blinding of treatments as well as inclusion of all methodological details in scientific publications is essential. In all preclinical sepsis studies, the high standards of animal welfare must be implemented. Therefore, development and validation of specific criteria for monitoring pain and distress, and euthanasia of septic animals, as well as the use of analgesics are recommended. A set of four considerations is also proposed to enhance translation potential of sepsis models. Relevant biological variables and comorbidities should be included in the study design and sepsis modeling should be extended to mammalian species other than rodents. In addition, the need for source control (in case of a defined infection focus) should be considered. These recommendations and considerations are proposed as "best practices" for animal models of sepsis that should be implemented.

Evaluation on case/problem-based and interactive teaching mode in pathophysiology curriculum / 中华医学教育探索杂志

Objectives@#To provide new ideas on how to shift students' learning attitude from passive learning to active learning, we explored and evaluated a case/problem-based and interactive teaching mode in pathophysiology curriculum.@*Methods@#Case/problem-based and interactive teaching mode is an innovative teaching model adopted in pathophysiology curriculum for grade 2015 students of 5-year program in clinical medicine and other medical students of non-clinical majors in Xiangya Medical School, Central South University. The teaching effectiveness of the case/problem-based and interactive teaching mode was evaluated by questionnaire survey, with 460 medical students enrolled in the survey whose approval degree on current teaching mode was analyzed. Excel was used to collect and process data, complete descriptive analysis and calculation of the percentage of indicators.@*Results@#A total of 460 anonymous questionnaires were distributed and 453 valid questionnaires were retrieved, from which the following information was obtained: ① Pre-class learners' guidance designed for current teaching mode: 88.7% of students (402/453) believed that "Pre-class Learners' Guidance" motivated them to preview relevant teaching contents before class. 82.8% of students (375/453) believed "Pre-class Learners' Guidance" improved discussion quality in class. 76.6% of students (347/453) believed "Pre-class Learners' Guidance" expanded thinking and exploring space, while it did not increase student study burden (306/453, 67.6%). ② Compared with traditional teaching mode, the case/problem-based and interactive teaching mode had following advantages: It's helpful to cultivate students' clinical thinking (414/453, 91.4%), strengthen students' memory and understanding during study (400/453, 88.3%), attract students' attention in class (380/453, 83.9%), and aroused student's interest in class discussion (327/453, 72.2%). ③ 83.4% of students (379/453) preferred current teaching mode: they believed this teaching mode could improve students' ability to analyze and solve problems (325/453,71.7%), train clinical thinking (321/453, 70.9%), improve students' self-study ability (247/453, 54.5%) and increase students' capabilities of making summary and conclusion (197/453, 43.5%).@*Conclusion@#Case/problem-based and interactive teaching mode in pathophysiology curriculum enhances students' ability of self-studying, activates classroom's atmosphere, improves teaching quality, and effectively fosters students' clinical thinking. Therefore, this teaching mode deserves to be spread and applied in classroom teaching of pathophysiology and other basic medicine disciplines as well.

Minimum quality threshold in preclinical sepsis studies (MQTiPSS): quality threshold for types of infections and organ dysfunction endpoints / 中华危重病急救医学

Although the clinical definitions of sepsis and recommended treatments are regularly updated, a systematic review has not been done for preclinical models. To address this deficit, a Wiggers-Bernard Conference on preclinical sepsis modeling reviewed the 260 most highly cited papers between 2003 and 2012 using sepsis models to create a series of recommendations. This PartⅡreport provides recommendations for the types of infections and documentation of organ injury in preclinical sepsis models. Concerning the types of infections, the review showed that the cecal ligation and puncture model was used for 44% of the studies while 40% injected endotoxin. Recommendation #8 (numbered sequentially from PartⅠ): endotoxin injection should not be considered as a model of sepsis; live bacteria or fungal strains derived from clinical isolates are more appropriate. Recommendation #9: microorganisms should replicate those typically found in human sepsis. Sepsis-3 states that sepsis is life-threatening organ dysfunction caused by a dysregulated host response to infection, but the review of the papers showed limited attempts to document organ dysfunction. Recommendation #10: organ dysfunction definitions should be used in preclinical models. Recommendation #11: not all activities in an organ/system need to be abnormal to verify organ dysfunction. Recommendation #12: organ dysfunction should be measured in an objective manner using reproducible scoring systems. Recommendation #13: not all experiments must measure all parameters of organ dysfunction, but investigators should attempt to fully capture as much information as possible. These recommendations are proposed as "best practices" for animal models of sepsis.

Minimum quality threshold in preclinical sepsis studies (MQTiPSS): quality threshold for types of infections and organ dysfunction endpoints / 中华危重病急救医学

Although the clinical definitions of sepsis and recommended treatments are regularly updated, a systematic review has not been done for preclinical models. To address this deficit, a Wiggers-Bernard Conference on preclinical sepsis modeling reviewed the 260 most highly cited papers between 2003 and 2012 using sepsis models to create a series of recommendations. This PartⅡreport provides recommendations for the types of infections and documentation of organ injury in preclinical sepsis models. Concerning the types of infections, the review showed that the cecal ligation and puncture model was used for 44% of the studies while 40% injected endotoxin. Recommendation #8 (numbered sequentially from PartⅠ): endotoxin injection should not be considered as a model of sepsis; live bacteria or fungal strains derived from clinical isolates are more appropriate. Recommendation #9: microorganisms should replicate those typically found in human sepsis. Sepsis-3 states that sepsis is life-threatening organ dysfunction caused by a dysregulated host response to infection, but the review of the papers showed limited attempts to document organ dysfunction. Recommendation #10: organ dysfunction definitions should be used in preclinical models. Recommendation #11:not all activities in an organ/system need to be abnormal to verify organ dysfunction. Recommendation #12: organ dysfunction should be measured in an objective manner using reproducible scoring systems. Recommendation #13: not all experiments must measure all parameters of organ dysfunction, but investigators should attempt to fully capture as much information as possible. These recommendations are proposed as "best practices" for animal models of sepsis.

Minimum quality threshold in preclinical sepsis studies (MQTiPSS): quality threshold for types of infections and organ dysfunction endpoints / 中华危重病急救医学

Although the clinical definitions of sepsis and recommended treatments are regularly updated, a systematic review has not been done for preclinical models. To address this deficit, a Wiggers-Bernard Conference on preclinical sepsis modeling reviewed the 260 most highly cited papers between 2003 and 2012 using sepsis models to create a series of recommendations. This PartⅡreport provides recommendations for the types of infections and documentation of organ injury in preclinical sepsis models. Concerning the types of infections, the review showed that the cecal ligation and puncture model was used for 44% of the studies while 40% injected endotoxin. Recommendation #8 (numbered sequentially from PartⅠ): endotoxin injection should not be considered as a model of sepsis; live bacteria or fungal strains derived from clinical isolates are more appropriate. Recommendation #9: microorganisms should replicate those typically found in human sepsis. Sepsis-3 states that sepsis is life-threatening organ dysfunction caused by a dysregulated host response to infection, but the review of the papers showed limited attempts to document organ dysfunction. Recommendation #10: organ dysfunction definitions should be used in preclinical models. Recommendation #11:not all activities in an organ/system need to be abnormal to verify organ dysfunction. Recommendation #12: organ dysfunction should be measured in an objective manner using reproducible scoring systems. Recommendation #13: not all experiments must measure all parameters of organ dysfunction, but investigators should attempt to fully capture as much information as possible. These recommendations are proposed as "best practices" for animal models of sepsis.

Minimum quality threshold in pre-clinical sepsis studies (MQTiPSS): quality thresholds for study design and humane modeling endpoints / 中华危重病急救医学

Preclinical animal studies are mandatory before new treatments can be tested in clinical trials. However, their use in developing new therapies for sepsis has been controversial because of limitations of the models and inconsistencies with the clinical conditions. In consideration of the revised definition for clinical sepsis and septic shock (Sepsis-3), a Wiggers-Bernard Conference was held in Vienna in May 2017 to propose standardized guidelines on preclinical sepsis modeling. The participants conducted a literature review of 260 most highly cited scientific articles on sepsis models published between 2003 and 2012. The review showed, for example, that mice were used in 79% and euthanasia criteria were defined in 9% of the studies. PartⅠof this report details the recommendations for study design and humane modeling endpoints that should be addressed in sepsis models. The first recommendation is that survival follow-up should reflect the clinical time course of the infectious agent used in the sepsis model. Furthermore, it is recommended that therapeutic interventions should be initiated after the septic insult replicating clinical care. To define an unbiased and reproducible association between a new treatment and outcome, a randomization and blinding of treatments as well as inclusion of all methodological details in scientific publications is essential. In all preclinical sepsis studies, the high standards of animal welfare must be implemented. Therefore, development and validation of specific criteria for monitoring pain and distress, and euthanasia of septic animals, as well as the use of analgesics are recommended. A set of four considerations is also proposed to enhance translation potential of sepsis models. Relevant biological variables and comorbidities should be included in the study design and sepsis modeling should be extended to mammalian species other than rodents. In addition, the need for source control (in case of a defined infection focus) should be considered. These recommendations and considerations are proposed as "best practices" for animal models of sepsis that should be implemented.

Evaluation on case/problem-based and interactive teaching mode in pathophysiology curriculum / 中华医学教育探索杂志

Objectives To provide new ideas on how to shift students' learning attitude from passive learning to active learning, we explored and evaluated a case/problem-based and interactive teaching mode in pathophysiology curriculum . Methods Case/problem-based and interactive teaching mode is an innovative teaching model adopted in pathophysiology curriculum for grade 2015 students of 5-year program in clinical medicine and other medical students of non-clinical majors in Xiangya Medical School, Central South University. The teaching effectiveness of the case/problem-based and interactive teaching mode was evaluated by questionnaire survey, with 460 medical students enrolled in the survey whose approval degree on current teaching mode was analyzed . Excel was used to collect and process data , complete descriptive analysis and calculation of the percentage of indicators. Results A total of 460 anonymous questionnaires were distributed and 453 valid questionnaires were retrieved , from which the following information was obtained: ①Pre-class learners' guidance designed for current teaching mode: 88.7％ of students (402/453) believed that"Pre-class Learners' Guidance"motivated them to preview relevant teaching contents before class . 82 . 8％ of students ( 375/453 ) believed "Pre-class Learners' Guidance" improved discussion quality in class. 76.6％ of students (347/453) believed "Pre-class Learners' Guidance" expanded thinking and exploring space, while it did not increase student study burden (306/453, 67.6％).②Compared with traditional teaching mode , the case/problem-based and interactive teaching mode had following advantages:It's helpful to cultivate students' clinical thinking (414/453, 91.4％), strengthen students' memory and understanding during study (400/453, 88.3％), attract students' attention in class (380/453, 83.9％), and aroused student's interest in class discussion (327/453, 72.2％). ③83.4％ of students (379/453) preferred current teaching mode: they believed this teaching mode could improve students' ability to analyze and solve problems (325/453,71.7％), train clinical thinking (321/453, 70.9％), improve students' self-study ability (247/453, 54.5％) and increase students' capabilities of making summary and conclusion (197/453, 43.5％). Conclusion Case/problem-based and interactive teaching mode in pathophysiology curriculum enhances students' ability of self-studying, activates classroom's atmosphere, improves teaching quality, and effectively fosters students' clinical thinking. Therefore, this teaching mode deserves to be spread and applied in classroom teaching of pathophysiology and other basic medicine disciplines as well.

Minimum quality threshold in preclinical sepsis studies (MQTiPSS): quality threshold for fluid resuscitation and antimicrobial therapy endpoints / 中华危重病急救医学

As outlined in the International Guidelines for Management of Sepsis and Septic Shock: 2016, initial fluid resuscitation and administration of antibiotics are key steps in the early management of sepsis and septic shock. However, such clear guidelines do not exist for preclinical sepsis models. To address these shortcomings, the Wiggers-Bernard conference on preclinical sepsis models was held in Vienna in May 2017. The participants reviewed 260 of the most highly cited papers between 2003 and 2012 that used sepsis models. The review demonstrated that over 70% of experiments either did not use or failed to report resuscitation and/or antibiotic treatment. This information served as the basis to create a series of recommendations and considerations for preclinical sepsis models; this Part Ⅲ report details the recommendations for fluid resuscitation and antibiotic treatment that should be addressed in sepsis models. Similar to human sepsis, fluid resuscitation is recommended in the experimental setting unless part of the study. Iso-osmolar crystalloid solutions are preferred. The administration route and its timing should be adjusted to the specific requirements of the model with preference given to dynamic rather than static hemodynamic monitoring. Predefined endpoints for fluid resuscitation and avoidance of fluid overload should be considered. Preclinical sepsis studies display serious inconsistencies in the use of antimicrobial protocols. To remedy this, antimicrobials are recommended for preclinical studies, with choice and dose adjusted to the specific sepsis model and pathogen(s). Ideally, the administration of antimicrobials should closely mimic clinical practice, taking into account the drug's pharmacokinetic profile, alterations in absorption, distribution and clearance, and host factors such as age, weight, and comorbidities. These recommendations and considerations are proposed as "best practices" for animal models of sepsis that should be implemented.

Minimum quality threshold in pre-clinical sepsis studies (MQTiPSS): an international expert consensus initiative for improvement of animal modeling in sepsis / 中华危重病急救医学

Preclinical animal studies precede the majority of clinical trials. While the clinical definitions of sepsis and recommended treatments are regularly updated, a systematic review of preclinical models of sepsis has not been done and clear modeling guidelines are lacking. To address this deficit, a Wiggers-Bernard Conference on preclinical sepsis modeling was held in Vienna in May, 2017. The goal of the conference was to identify limitations of preclinical sepsis models and to propose a set of guidelines, defined as the "Minimum Quality Threshold in Pre-clinical Sepsis Studies" (MQTiPSS), to enhance translational value of these models. A total of 31 experts from 13 countries participated and were divided into six thematic Working Groups: Study Design, Humane modeling, Infection types, Organ failure/dysfunction, Fluid resuscitation, and Antimicrobial therapy endpoints. As basis for the MQTiPSS discussions, the participants conducted a literature review of the 260 most highly cited scientific articles on sepsis models (2003-2012). Overall, the participants reached consensus on 29 points; 20 at "recommendation" and nine at "consideration" strength. This Executive Summary provides a synopsis of the MQTiPSS consensus. We believe that these recommendations and considerations will serve to bring a level of standardization to preclinical models of sepsis and ultimately improve translation of preclinical findings. These guideline points are proposed as "best practices" for animal models of sepsis that should be implemented. To encourage its wide dissemination, this article is freely accessible on the Intensive Care Medicine Experimental and Infection journal websites. In order to encourage its wide dissemination, this article is freely accessible in Shock, Infection, and Intensive Care Medicine Experimental.

Role of nucleolin on myocardial hypertrophy and fibrosis in type II diabetic cardiomyopathy mice / 中国病理生理杂志

AIM: To investigate the effect of nucleolin on diabetic cardiomyopathy in mice.METHODS: A type II diabetic cardiomyopathy mouse model was prepared using a cardiac-specific nucleolin-overexpressing transgenic mice.The mice were divided into wild-type mouse control group, nucleolin transgenic mouse control group, wild-type mouse diabetes group and nucleolin transgenic mouse diabetes group.Wheat germ agglutinin (WGA) fluorescent dye, Masson staining and PowerLab system detection were used to further clarify the role of nucleolin on cardiac hypertrophy, fibrosis and cardiac function in type II diabetic cardiomyopathy mice.RESULTS: Compared with wild-type mouse control group, no significant increase in blood glucose level was found, while genetical myocardial cell hypertrophy was significantly attenuated in nucleolin transgenic mouse diabetes group.The collagen fibers were also significantly reduced, and hemodynamic indexes ± dp/dtmax, left ventricular end-diastolic pressure, left ventricular systolic pressure and heart rate were also improved.The above differences were statistically significant.CONCLUSION: Nucleolin may reduce the occurrence of myocardial hypertrophy and fibrosis, thus improving the cardiac function of diabetic cardiomyopathy mice.

Effect of nucleolin on cardiac cell apoptosis in Type 2 diabetic cardiomyopathy mice / 中南大学学报(医学版)

Objective:To investigate the effect of nucleolin on cardiac cell apoptosis in Type 2 diabetic cardiomyopathy mice.Methods:Mice were fed with high-fat and high-sugar food for 20 weeks (mice were injected intraperitoneally with 60 mg/kg streptozotocin in the 5th and 6th weeks) to establish a mouse model of Type 2 diabetes.The mice were divided into 4 groups:a wild type (WT) control group,a nucleolin transgenic (TG) control group,a WT diabetic group,a TG diabetic group.Diabetesrelated indicators were detected at the end of the 8th week.At the end of the 20th week,HE staining was used to observe myocardial morphological changes;TUNEL staining and caspase-3 activity were used to detect the extent of apoptosis of cardiac myocytes.Results:The level of fasting blood glucose was significantly increased in the diabetic group than that in the control group.In WT diabetic group,myocardial disarrangement,fragmentation and dissolution were observed (determined by HE staining);cellular apoptosis (determined by TUNEL staining and caspase-3 activity) also increased markedly in the WT diabetic group.Compared with the wild mice in the diabetic group,myocardial morphological changes and cardiac myocytes apoptosis were alleviated significantly.Conclusion:Nucleolin overexpression affectes the occurrence and development of diabetic cardiomyopathy through inhibition of cardiac myocyte apoptosis.

Teaching effectiveness evaluation on classroom-site segmented discussions of a patient case in inter-nal environment system / 中华医学教育探索杂志

Objective To provide reliable reference for improving teaching methods of case discus-sion, the teaching effectiveness evaluation on classroom-site segmented discussions of a patient case was completed in internal environment system. Methods The questionnaire survey was conducted among 250 clinic students of 8-year program and of 5-year program to investigate the teaching effectiveness following implementation of the teaching plan called"classroom-site segmented study of patient case debate competi-tion seminars". The contents of questionnaire survey included: the students' view on characteristics and advantages of this teaching plan and the reasons for favoring and supporting the plan. Investigation was conducted using an anonymous questionnaire. A total of 250 questionnaires were distributed and 247 valid questionnaires retrieved. Data collection and analysis were performed by using Excel and SPSS 17.0 statistical software, percentage of each observing parameter was calculated. Results ①The students' view on ad-vantages of the plan included following: reducing students' study burden by 78.5％ (194/247), increasing the students' engagement in class activities by 85.4％(211/247), improving teaching quality in class discus-sion by 80.5％ (198/246), enhancing team spirit among students by 78.5％ (194/246), expanding students' thinking and exploring space by 84.5％ (207/245), and similarity of this teaching plan to clinical diagnosis and treatment process reached to 84.0％(197/235). ②The students' reasons for favoring and supporting this plan included: reducing students' study burden by 83.4％ (206/247), improving teaching quality in class discussion by 72.4％(179/247), and training students' ability to search clinical information by 82.4％ (203/247). Conclusion Implementation of the teaching plan, "classroom-site segmented study of patient case debate competition seminars", in internal environment system has reduced students' study burden, improved teaching quality, and effectively trained students' clinic thinking, which is widely welcomed by students, therefore providing a positive valuable reference to other discussion class.

Protective effect of Allicin on intestinal mucosal barrier of septic rats / 中华急诊医学杂志

Objective To investigate the protective effect of allicin on intestinal mucosal barrier of septic rats so as to explore the possible mechanism.Methods Twenty-four male SD rats were randomly (random number) divided into sham,septic model and allicin treatment group.Septic model was established by cecal ligation and puncture (CLP) in rats.Rats in the treatment group were administered with allicin (30 mg/kg,ip)at 6 h and 12 h after modeling,while those in the model and sham groups were treated with equal amount of saline instead.Rats were sacrificed at 24 h and the serum D-lactic acid,diamine oxidase (DAO) and fluorescence isothiocyanate-dextran (FITC-Dextran,FD-40) were determined to evaluate the intestinal mucosal barrier function.The levels of tumor necrosis factor-α (TNF-α),interleukin-6 (IL-6),malondialdehyde (MDA),and the activity of superoxide dismutase (SOD) in intestinal tissue were measured.Histopathological changes of intestinal mucosa injury were assessed by Hematoxylin-eosin staining.Results Compared with the sham group,levels of serum D-lactic acid,DAO and FD-40 increased significantly in the CLP group (D-lactic acid:599.4±101.1 vs.149.2±20.63 nmoL/mL,t=11.84,P＜0.01;DAO:302.1 ±64.5 vs.76.57±14.76 ng/mL,t=9.433,P＜0.01;FD-40:6664.0±1437.0vs.1446.0±205.0 ng/mL,t =9.704,P ＜0.01);intestinal morphology damage occurred in the CLP group;intestinal levels of TNF-α,IL-6 and MDA increased greatly (TNF-αt:186.35 ±20.43 vs.58.76 ±8.94 pg/mL,t=17.23,P＜0.01;IL-6:763.25±85.23vs.125.36±14.37 pg/mL,t=22.54,P＜0.01;MDA:29.36±3.27vs.7.24±0.85 nmol/mg prot,t=16.61,P＜0.01),while SOD activity reduced (35.75±6.53 vs.73.26 ±8.35 U/rmg prot,t =10.57,P ＜0.01) in the CLP group.Allicin treatment greatly inhibited the increase of D-lactic acid,DAO and FD-40 levels in rat plasma caused by CLP (D-lactic acid:330.1 ±81.77 vs.599.4±101.1 nmol/mL,t=7.086,P＜0.01;DAO:171.8±49.70vs.302.1±64.56ng/mL,t=5.45,P＜0.01;FD-40:3349.0±1167.0 vs.6664.0±1437.0 ng/mL,t=6.165,P＜0.01);intestinal morphology damage was improved in the allicin treatment group;allicin treatment greatly inhibited the intestinal levels of TNF-o,IL-6 and MDA and preserved the intestinal SOD activity compared with the CLP group (TNF-α:95.37 ±12.68 vs.186.35 ±20.43 pg/mL,t =12.29,P＜0.01;IL-6:354.27±46.27vs.763.25±85.23pg/mL,t=14.45,P＜0.01;MDA:16.27±3.14vs.29.36±3.27 nmol/mgprot,t=9.831,P＜0.01;SOD:55.35 ±6.23vs.35.75±6.53 U/mgprot,t=5.522,P ＜0.01).Conclusions Allicin could inhibit local inflammation and oxidative stress in the intestine and exerts protective effect on intestinal mucosal barrier of septic rats.

Measurement of serum lipopolysaccharide binding protein for diagnosis and prognosis prediction in septic patients / 中国病理生理杂志

AIM:To investigate the role of lipopolysaccharide binding protein (LBP) for diagnosis and prog-nosis prediction in the septic patients.METHODS:A total number of 80 ICU patients were enrolled.The patients were divided into systemic inflammatory response syndrome ( SIRS) group and sepsis group, the patients in sepsis group were di-vided into non-survivor sub-group and survivor sub-group.We collected the serum samples and analyzed acute physiology and chronic health evaluation ( APACHE) II score on the first day of the patients hospitalized in ICU.In addition, we also selected 10 healthy volunteers and collected their serum samples.The serum concentrations of LBP, C-reactive protein ( CRP) and procalcitonin ( PCT) were measured by ELISA.ROC analysis of LBP, CRP, PCT and APACHE II score was conducted to discriminate among critically ill patients with sepsis and predict the prognosis of the patients with sepsis.RE-SULTS:The levels of the 4 indicators in the septic patients were higher than those in the patients of SIRS (P<0.05).In addition, serum LBP and APACHE II score in the non-survivor sub-group were higher than those in the survivor sub-group (P<0.05), whereas no difference of the PCT and CRP levels between survivors and non-survivors with sepsis was ob-served.LBP levels greater than 26.84 mg/L had 97.1% sensitivity and 95.9% specificity to discriminate between SIRS and sepsis.LBP levels greater than 54.16 mg/L had 85.2%sensitivity and 80.0%specificity for prognosis of unfavorable outcome.CONCLUSION:LBP level was more accurately correlated with diagnosis or prognosis prediction than CRP or PCT in patients with sepsis.

Establishment and identification of myocardium-specific nucleolin trans-genic mice / 中国病理生理杂志

AIM:To construct myocardium-specific nucleolin ( Ncl) transgenic mice and to provide an animal model for the studies of the myocardial protection of nucleolin .METHODS:To create nucleolin transgenic mice , a myo-cardium-specific expression plasmid of nucleolin ( Alpha-MyHC clone 26-Ncl) was constructed .The gene type of transgenic mice was identified by PCR and the nucleolin protein level was tested by Western blotting .The myocardium morphology , heart weight index (HWI) and left ventricular pressure maximum rise rate were observed in nucleolin transgenic (TG) mice and wild-type ( WT) mice.RESULTS:We gained 4 transgenic mice (51, 52, 56 and 86 lines, only 52 line and 86 line were eugonic) by PCR.Western blotting analysis showed the expression of nucleolin up-regulated specifically in the myocardium .However , the myocardium morphology , HWI and left ventricular pressure maximum rise rate in the nucleolin transgenic mice were similar to those in the wild-type mice.CONCLUSION:We constructed myocardium-specific nucleo-lin transgenic mice successfully .

Nucleolus expression in diabetic cardiomyopathy / 中南大学学报(医学版)

OBJECTIVE@#To investigate the nucleolus expression in the diabetic cardiomyopathy.@*METHODS@#The rats were divided into a control group and a type II diabetic cardiomyopathy group (model group). In the model group, rats were fed with high-fat and high-sugar food (rats were intravenously injected with 60 mg/kg chain urea with cephalosporins in the 5th and 6th weeks in mice). The level of blood glucose was determined at the end of 8th week and the level of fasting blood glucose was examined at the end of 20th week. The ratio of the heart mass and body mass was calculated, and the pathological changes in myocardial morphology were observed. The immunohistochemical method and Western blot were used to detect the expression level of myocardial nucleolin.@*RESULTS@#The level of fasting blood glucose was significantly increased in the diabetic model group than that in the control group (P<0.05). Rats in the model group were found hypertrophic cardic cells, with fracture, dissolusion, and disordered arrangement. Immunohistochemical staining and Western blot showed the protein levels of myocardial nucleolin in the model group were obviously higher than those in the control group (P<0.05).@*CONCLUSION@#Nucleolin may play a role in the pathogenesis and development of the diabetic cardiomyopathy.

Expression of nucleolin in pressure overload-induced cardiac hypertrophy rats / 中南大学学报(医学版)

OBJECTIVE@#To detect the expression of nucleolin in cardiac hypertrophy rats induced by pressure overload.@*METHODS@#A total of 40 SD rats with body weight 180 g and 220 g were recruited and randomly divided into 2 groups: a transverse aortic constriction (TAC) group and a sham surgery group. Cardiac hypertrophy model was employed by transverse aortic constriction surgery. Then 2 weeks and 4 weeks after the experiment, the heart mass index (HMI), left ventricle mass index (LVMI) were measured. β-MHC mRNA in the heart tissue was detected with RT-PCR. Nucleolin in the heart, brain and kidney was respectively detected with Western blot.@*RESULTS@#Compared with the sham surgery group, HMI, LVMI in the TAC group increased significantly (P<0.01) 4 weeks after the surgery; the expression of β-MHC mRNA in the heart tissue increased (P<0.05) in the TAC group 4 weeks after the surgery; and the expression of nucleolin protein in the heart tissue of the TAC group was remarkably upregulated (P<0.05) 2 weeks after the surgery, with no change in the brain and kidney tissue between the 2 groups.@*CONCLUSION@#Expression of nucleolin protein has been upregulated in response to pressure overload, which may suggest that nucleolin plays a role in cardiac hypertrophy induced by pressure overload.

The plasmic translocation and release of high mobility group box chromosomal protein 1 in peripheral blood monocytes of patients with rheumatoid arthritis and the effect of thalidomide / 中华内科杂志

Objective To investigate the release and intracellular localization of high mobility group box chromosomal protein 1(HMGBl)in the peripheral blood monocytes of rheumatoid arthritis(RA) patients and the inhibitive effect of thaiidomide.Methods 19 RA patients and 20 healthy controls were included in the study.Monocytes were separated from peripheral blood with Ficoll density gradient centrifugation.Monocytes were treated with 100 ng/ml tumor necrosis factor α(TNFa)or 100 ng/ml TNFα plus 40 μg/ml thalidomide and grown in an incubator at 37℃ with 5%CO,for 24 hours.The cuIture supernatants of the monocytes were collected.HMGB1 level in the culture medium was detected with Western blot.In addition,the intraceUular localization of HMGB1 in the fflonocytes was investigated with immunocytochemical analysis. Results Without stimulation. the release of HMGBl protein was significantly increased in the culture supernatants of peripheral blood monocytes from RA patients as compared with that from healthy controls(P<0.05).TNFα(100 ng/ml)did not further increase the release of HMGBl in the monocytes from the patients with RA.Thalidomide(40 μg/ml)could inhibit the release of HMGB1 in the monocytes from RA patients stimulated with TNFα(P<0.05).In the monocytes from RA patients,HMGBl was mainly localized in the nucleus.Treatment with TNFOL(100 ng/ml)for 24 hour resulted in a cytoplasmic translocation of HMGB1,which was inhibited significantly by thalidomide. Conclusion TNFα induces the release and cytoplasmic translocation of HMGBI in the peTipheral blood monocytes of RA patients and thalidomide inhibits the release and translocation of HMGB1.

The Actuality Analysis and Reform Exploration in Theory Pedagogy of Pathophysiology / 中华医学教育探索杂志

As the national key discipline and the best national course,the department of pathophysiology in Central South University has carried out a series of teaching reforms in order to improve the students' innovative ability.In this article,the authors,five-year system medical students of Xiangya School of Medicine,make a research on students' view of these reforms,aiming at analyzing the effects of these reforms correctly and put forward some suggestions on the basis of their own study experiences.