Oleanolic acid (OA), a pentacyclic triterpenoid, exhibits a broad spectrum of biological activities, including antitumor, antiviral, antibacterial, anti-inflammatory, hepatoprotective, hypoglycemic, and hypolipidemic effects. Since its initial isolation and identification, numerous studies have reported on the structural modifications and pharmacological activities of OA and its derivatives. Despite this, there has been a dearth of comprehensive reviews in the past two decades, leading to challenges in subsequent research on OA. Based on the main biological activities of OA, this paper comprehensively summarized the modification strategies and structure-activity relationships (SARs) of OA and its derivatives to provide valuable reference for future investigations into OA.
Oleanolic Acid ; Structure-Activity Relationship ; Anti-Inflammatory Agents/pharmacology* ; Triterpenes ; Anti-Bacterial Agents/pharmacology*

Objective:To understand the frailty status of the elderly in nursing homes and analyze its influencing factors.Methods:This study is a cross-sectional study. Using the convenient sampling method, a total of 266 elderly people in 6 nursing homes in Changsha city were selected from April to October 2019. General information questionnaire, Chinese version of Tilburg Frailty Scale, Mini-Mental State Examination (MMSE) , Pittsburgh Quality Index (PSQI) , UCLA Loneliness Scale, Geriatric Depression Scale (GDS-5) and Social Support Rating Scale (SSRS) were used to investigate. Multiple linear regression was used to analyze the influential factors of frailty in the elderly.Results:Totally 266 questionnaires were distrionted, and 265 questionnaires were valid. The frailty score of the elderly in nursing homes was (6.97±3.64) and the detection rate of frailty was 59.2% (157/265) . The results of single factor analysis showed that there were statistically significant differences in the total frailty scores of elderly people with different education levels, nature of nursing homes, retirement income, number of falls, weight category, physical activities, intelligent training, social activities and self-rated health status ( F/t=24.541, 2.265, 17.404, 15.311, 4.193, 35.574, 21.376, 6.957, 53.135; P<0.05) . The results of correlation analysis showed that sleep quality, loneliness and depression were positively correlated with frailty and its dimensions ( P<0.01) , while cognitive function and social support were negatively correlated with frailty and its dimensions ( P<0.01) . The results of multiple linear regression analysis showed that the number of falls, self-rated health status, depression score and loneliness score could positively predict the overall frailty score (standardized regression coefficients were 0.112, 0.171, 0.280, 0.241; P<0.01) , while physical activity, cognitive function score could negatively predict overall frailty scores (standardized regression coefficients were -0.165, -0.174; P<0.01) . Conclusions:The current status of frailty of the elderly in nursing homes is not optimistic. The elderly need to improve the evaluation of elderly frailty and carry out early intervention for high-risk elderly people to delay the process of frailty.

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.

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.

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.

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.
Animals ; Anti-Bacterial Agents/therapeutic use* ; Fluid Therapy ; Humans ; Practice Guidelines as Topic ; Resuscitation ; Sepsis/therapy* ; Shock, Septic

Objective    To compare the effects of transthoracic device closure and surgical closure on ventricular septal defect systemically. Methods    A systematic literature search was conducted using the PubMed, EMbase, The Cochrane Library, VIP, CNKI, CBM, Chinese Clinical Trial Register, ClinicalTrials. gov and Wanfang Database up to July 31, 2016. Quality was assessed and data of included articles were extracted. The meta-analysis was conducted using RevMan 5.0 and Stata 14.0 software. Results    Eleven studies were identified, including 5 RCTs and 6 cohort studies involving 2 504 patients. For success rate, there was no statistical difference between the transthoracic closure group and the surgical closure group in RCT (RR=0.99, 95%CI 0.96 to 1.03, P=0.70); the success rate in the transthoracic closure group was lower than that in the surgical closure group in the cohort study (OR=0.21, 95%CI 0.08 to 0.55, P=0.002). Both  results of RCTs and cohort studies showed that compared with surgical closure, transthoracic device closure reduced duration of the operation (RCT MD=–79.38, 95%CI –95.00 to –63.76, P<0.000 01; cohort study MD=–66.26, 95%CI –71.20 to –61.31, P<0.000 01) and hospital stay (RCT MD=–2.10, 95%CI –2.65 to –1.55, P<0.000 01; cohort study MD=–3.99, 95%CI –6.03 to –1.94, P=0.000 1), and the patients with blood transfusion (RCT RR= 0.04, 95%CI 0.01 to 0.11, P<0.000 01; cohort study OR=0.01, 95%CI 0.00 to 0.13, P=0.001). In the transthoracic closure group the risk of postoperative arrhythmia reduced (RCT RR=0.20, 95%CI 0.13 to 0.32, P<0.000 01; cohort study OR=0.46, 95%CI 0.31 to 0.67, P<0.000 1). In the transthoracic closure group a higher postoperative valvular regurgitation risk in RCT induced (RR=1.45, 95%CI 1.07 to 1.96, P=0.02) and the rate of postoperative valvular regurgitation in cohort study reduced (OR=0.43, 95%CI 0.20 to 0.92, P=0.03). However, there was no statistical difference in postoperative residual shunt (RCT RR=0.96, 95%CI 0.57 to 1.62, P=0.89; cohort study OR=0.52, 95%CI 0.12 to 2.25, P=0.38). Conclusion    Transthoracic device closure can shorten duration of the operation, hospital stay and reduce the patients with blood transfusion and post- and intraoperative arrhythmia risk. Therefore, transthoracic device closure may be a better approach for some ventricular septal defect patients.

Objective To study the effect of lithium chloride on the gap junction in the myocardium under chronic hypoxia.Methods Twenty-five C57BL/6J mice were randomly divided into normoxia group,hypoxia group,normoxic control group,hypoxia + saline group and hypoxia + lithium chloride group.Hypoxia group was treated with 10％ oxygen concentration for 4 weeks.Hypoxia + saline group and hypoxia + lithium chloride group were intraperitoneal injection of saline and lithium chloride.Electrophysiology and cardiac catheterization were used to assess arrhythmias,heart rate and ejection fraction.The expression of Cx43,phosphorylated glycogen synthase kinase 3β(p-GSK-3β) and glycogen synthase kinase 3β (GSK-3β) were detected by Western blot.Results Compared with the normoxia group,the hypoxia group had a faster heart rate [(448 ± 18) bpm vs.(401 ± 13) bpm,P＜0.05),and the ejection fraction was decreased [(56±5)％ vs.73±4)％,P＜0.05],arrhythmia score increased [(3.4±0.5)％ vs.(0.6±0.5)％,P＜0.05],Cx43 expression was decreased.Compared to hypoxia + normal saline group,the heart rate decreased[(412±11)bpm vs.(454±18)bpm,P＜0.05],ejection fraction increased[(69±3)％ vs.(55±4)％,P＜0.05],the score of arrhythmia decreased [(1.8±0.4) ％ vs.(3.0±0.7)％,P＜0.05] in hypoxia + lithium chloride group,the expression of Cx43 and the rate of p-GSK-3β to GSK-3β were increased.Conclusion During the chronic hypoxia,lithium chloride can sustain the gap junction through inhibition of GSK-3β signaling way,which can also reduce the rate of arrhythmia.

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.

Objective To explore the diagnostic value of Talaromyces marneffei (T.marneffei)-specific mannose glycoprotein Mp1p antigen for T.marneffei infection in acquired immune deficiency syndrome (AIDS) patients.Methods All cases were recruited in this study from January 2012 to June 2015 in Guangzhou No.8 People′s Hospital, including 184 AIDS patients with T.marneffei infection confirmatively diagnosed by culture, and 205 controls including 176 AIDS patients without T.marneffei infection and 29 health controls.Double antibody sandwich enzyme linked immunosorbent assay and fluoroimmunoassay combined with double-antibody sandwich were both utilized to detect serum Mp1p antigen levels, and their sensitivity and specificity for diagnosing T.marneffei infection in patients with AIDS were analyzed.x2 test and t test were used for statistical analysis.Results The ratio of males to females and age of the study group were both comparable to those of the control group (x2=0.019, P=0.889;t=1.810,P=0.07, respecitvley).The sensitivities of double antibody sandwich enzyme linked immunosorbent assay and fluoroimmunoassay combined with double-antibody sandwich were 82.07%(151/184) and 83.15%(153/184), respectively (x2=0.076, P=0.783).The specificities were 93.17%(191/205) and 92.68%(190/205), respectively (x2=0.037, P=0.847).The accuracy values were 87.92%(342/389) and 88.17%(343/389), respectively (x2=0.012, P=0.912).The false positive rates were 6.83%(14/205) and 7.32%(15/205), respectively.The false negative rates were 17.93%(33/184) and 16.85%(31/184), respectively (x2=0.049, P=0.829).The positive predictive values were 91.52%(151/165) and 91.07%(153/168), respectively (x2=0.021, P=0.886).The negative predictive values were 85.27%(191/224) and 85.97%(190/221), respectively (x2=0.045, P=0.832).The Kappa values were 0.83 and 0.80, respectively.Conclusion Detection of serum Mp1p antigen of T.marneffei possesses high specificity and sensitivity, which may be utilized for rapid and early diagnosis of T.marneffei infection in patients with AIDS.