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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.
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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.
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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.
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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.
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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.
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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.
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Objective To explore the value of serum microRNA-155-5p and -133a-3p (miR-155-5p and miR-133a-3p) expression for the diagnosis and prognosis evaluation of sepsis. Methods A prospective observational study was conducted. 105 sepsis patients admitted to emergency intensive care unit (EICU) of the First Affiliated Hospital of Zhengzhou University from January 2015 to January 2016 were enrolled. They were divided into three groups according to the severity: 35 patients with sepsis, 35 with severe sepsis, and 35 with septic shock. At the same time, 35 healthy persons were selected as the control group. According to the prognosis, the patients were divided into improved group (n = 70) and in-hospital death group (n = 35). The clinical data of all the subjects were collected. The mRNA expressions of miR-155-5p and miR-133a-3p were determined by reverse transcription-polymerase chain reaction (RT-PCR). The receiver-operating characteristic curve (ROC) was plotted to evaluate their clinical value for the diagnosis and prognosis of sepsis. The binary logistic regression was used to analyze the risk factors affecting the prognosis of sepsis patients. Results ① The mRNA expressions of serum miR-155-5p and miR-133a-3p were gradually increased with the aggravation of sepsis. The mRNA expression of miR-155-5p (2-ΔCt) in sepsis, severe sepsis, sepsis shock groups was 1.89±0.48, 2.21±0.41, 2.79±0.73 (F = 23.737, P = 0.000), and the mRNA expression of miR-133a-3p (2-ΔCt) was 1.38±0.31, 1.74±0.65, 2.08±0.47, respectively (F = 27.710, P = 0.000). It was shown by ROC curve analysis that the area under the ROC curve (AUC) of serum miR-155-5p and miR-133a-3p for the diagnosis of sepsis was 0.855 [95% confidence interval (95%CI) = 0.761-0.949] and 0.769 (95%CI = 0.666-0.872) respectively. The cut-off value of miR-155-5p for the diagnosis of sepsis was 1.64, the sensitivity was 85.3%, and specificity was 80.6%. While the cut-off value of miR-133a-3p was 0.82, the sensitivity and specificity were 97.9% and 54.8% respectively. ② Compared with improved group, the patients of in-hospital death group were more serious, and procalcitonin (PCT), C-reactive protein (CRP), D-dimer, lactic acid (Lac), sequential organ failure assessment (SOFA) score, acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ) score, and the mRNA expressions of miR-155-5p and miR-133a-3p were significantly increased (all P 0.05). It was shown by binary logistic regression analysis that Lac [odds ratio (OR) = 0.514, 95%CI = 0.260-0.893, P = 0.024], sepsis severity (OR = 0.039, 95%CI = 0.023-2.955, P = 0.016), SOFA score (OR = 0.668, 95%CI = 0.474-0.825, P = 0.001), serum miR-155-5p expression (OR = 0.117, 95%CI = 0.020-0.530, P = 0.007) were the risk factors affecting the prognosis of patients with sepsis. Conclusions The expression of serum miR-155-5p and miR-133a-3p may be used as specific indicators for the diagnosis of sepsis. And the expression of miR-155-5p can be used as independent impact factor for the estimation of sepsis prognosis.
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Objective:To study the changes and significance of Th17 and Treg cells as well as their associated cytokines in pe-ripheral blood of patients with chronic hepatitis C and cirrhosis in order to investigate their role in the pathogenesis of chronic hepatitis C and hepatitis C cirrhosis. Methods:Flow cytometry and ELSIA assay were used to detect the expression ratio of Th17 and Treg cells and the serum levels of IL-10,TGF-β,IL-6 and IL-17 in peripheral blood of healthy human and patients with chronic hepatitis C and hepatitis C cirrhosis. Than we analyzed the differences of the above detection index between the healthy and patients with chronic hepatitis C and hepatitis C cirrhosis. Results:The expression ratio of Th17 cells (1. 33%±0. 30%) in peripheral blood of patients with chronic hepatitis C and IL-6[(8. 10±2. 42)ng/L] and IL-17[(16. 70±4. 73)ng/L] serum levels were significantly higher than those in the healthy (Th17:1. 14%±0. 19%) and IL-6[(1. 72±6. 70)ng/L],IL-17[(12. 29±1. 88)ng/L],P<0. 05;The expression ratio of Treg cells in peripheral blood of patients with hepatitis C cirrhosis and chronic hepatitis C patients was significantly higher than that in the healthy (6. 21%±0. 76%,5. 89%±0. 85% vs 5. 51%±0. 59% ),P<0. 05,The ratio of Th17/Treg in patients with cirrhosis was significantly lower than that in patients with chronic hepatitis C and the healthy(0. 19±0. 02 vs 0. 22±0. 03,0. 21±0. 03),P<0. 05;the levels of IL-1[(16. 21±3. 76)ng/L] and TGF-β[(5. 15±0. 83)ng/L] in peripheral blood of patients with hepatitis C cirrhosis were significantly higher than those in chronic hepatitis C[(14. 36±2. 78)ng/L;(4. 47±0. 87)ng/L] and the healthy[(14. 01±3. 01)ng/L;(4. 43±0. 98)ng/L)],P<0. 05. Conclusion:Th17 and Treg cells and their related cytokines involved in the process of chronicity of hepatitis C and cirrhosis,Th17 and Treg cells and their related cytokines in the treatment and prevention of chronicity of hepatitis C and cirrhosis may have important significance.
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Objective:To study of change of Th17 cell and IL-17 caused by bacteria biofilm after infection.Methods: To detect biofilm formation ability of bacteria isolated from bronchus alveolus washing-water of patients;to detect expressing ratios of Th17 cells and IL-17 level in peripheral blood of patients and healthy person;to detect expressing ratios of Th17 cells and IL-17 level in bronchus alveolus washing-water of patients;to analyze the above data using SPSS17.0 software.Results: Expressing ratios of Th17 cells and IL-17 level in peripheral blood of patients infected by producing biofilm and non-producing biofilm bacteria and healthy person are respectively(0.59±0.18)%and(108.8±20.5)pg/ml,(0.58±0.18)%and(100.1±20.7)pg/ml,(0.55±0.17)% and(100.0± 21.4)pg/ml,they were not different among data from patients and healthy person,P>0.05,expressing ratios of Th17 cells and IL-17 level in bronchus alveolus washing-water of patients infected by producing biofilm and non-producing biofilm bacteria were respective (1.37±0.34)%,(157.4±30.8)pg/ml and(1.11±0.21)%,(136.2±24.3)mg/ml,the data between patients infected by producing biofilm and non-producing biofilm bacteria were distinctly different, P<0.05.Conclusion: Bacteria biofilm can cause Th17 cell expressing ratio and IL-17 level to become high in infected part,this may be mechanism that infection become chronic.
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Objective To construct a questionnaire for patients to participate in hand hygiene promotion in medical institutions,and provide a measuring tool for patients to participate in hand hygiene promotion.Methods A ques-tionnaire was constructed by methods of literature research,expert panel discussion,pre-investigation,and Delphi. Results This questionnaire was designed respectively for patients and health care workers,each contained 20 ques-tions,involving hand hygiene perception,willingness to participate in promoting hand hygiene,and participation method,et al.Conclusion A questionnaire for patients to participate hand hygiene promotion in medical institutions is preliminary constructed,which can be used for evaluating patients’and HCWs’willingness and relevant influen-cing factors of patients’participation in hand hygiene promotion in medical institutions.
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The elasticity of the ascending aorta in healthy volunteers and hypertension patients were examined by using quantitative tissue velocity imaging (QTVI), and the age-related change in the ascending aortic elasticity was investigated. The anterior and posterior walls of the ascending aorta were imaged with tissue Doppler method in all the subjects and QTVI was performed. Stable curves were obtained from 173 hypertension patients and 185 healthy adults. The peak early diastolic velocity (V(e)), peak late diastolic velocity (V(a)) and peak systolic velocity (V(s)) were measured. The relation of age with these measures was assessed. The results showed that the elasticity of the ascending aorta was much lower in the hypertension patients than in normal controls (P<0.05), and the elasticity was decreased with age in both groups (P<0.05). Our results suggested that QTVI, a new non-invasive ultrasonic technique, is helpful for the assessment of the aortic elasticity in hypertension patients.
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<p><b>OBJECTIVE</b>To clone a novel human connexin gene and find out the relationship between this gene and hereditary deafness.</p><p><b>METHODS</b>Through the basic local alignment search tool (BLAST) analysis against the database of expressed sequence tags (dbEST) of National Center for Biotechnology Information (NCBI) using the coding sequence of mouse Cx 57 gene, 9 novel ESTs were obtained and a contig was assembled. Nested polymerase chain reaction (PCR) and rapid amplification of cDNA ends (RACE) were performed using primers designed on the contig. A novel gene was obtained and was mapped by homologous analysis against human genome sequence. Mutation analysis was performed in 12 autosomal dominant hereditary deafness families.</p><p><b>RESULTS</b>Nine ESTs were obtained by homologous analysis and a contig was assembled. Through nested PCR and RACE, a full length of cDNA was obtained from human liver, kidney Ready cDNA and placenta cDNA library, and was named CX 58. By comparison with human genome sequence, CX 58 was mapped at 1p32.3-p34.1. Mutation analysis of CX 58 was performed in 12 autosomal dominant hereditary deafness families, but no mutation was detected.</p><p><b>CONCLUSION</b>A novel human connexin gene named CX 58 was cloned and mapped to 1p32.3-p34.1. The mutation of CX 58 may not result in autosomal dominant hereditary deafness.</p>
Subject(s)
Animals , Female , Humans , Mice , Chromosome Mapping , Chromosomes, Human, Pair 1 , Genetics , Cloning, Molecular , Connexins , Genetics , DNA, Complementary , Chemistry , Genetics , Expressed Sequence Tags , Molecular Sequence Data , Sequence Alignment , Sequence Analysis, DNAABSTRACT
To compare the chemical components of supercritical extracts from Herba Ephedrae and honey-prepared Herba Ephedrae. Volatile oils were extracted from Herba Ephedrae and honey-prepared Herba Ephedrae by supercritical CO 2 extraction and then identified by the combination of gas chromatography and mass spectrometry (GC-MS). Twenty kinds of components such as diethylsulfate obtained from Herba Ephedrae were not found in honey-prepared Herba Ephedrae and twelve different components such as hydroxymethylfurfural were obtained from honey-prepared Herba Ephedrae. The extraction rate of volatile oils was 2.1% in herba ephedrae and 1.0% in honey-prepared Herba Ephedrae. [ Conclusion]The components of supercritical extractions from Herba Ephedrae differ from those in honey-prepared Herba Ephedrae.