Establishment and evaluation of animal models of sepsis-associated encephalopathy

BACKGROUND:Sepsis-associated encephalopathy(SAE) is a critical disease caused by sepsis.In addition to high mortality,SAE can also adversely aff ect life quality and lead to significant socioeconomic costs.This review aims to explore the development of evaluation animal models of SAE,giving insight into the direction of future research in terms of its pathophysiology and therapy.METHODS:We performed a literature search from January 1,2000,to December 31,2022,in MEDLINE,PubMed,EMBASE,and Web of Science using related keywords.Two independent researchers screened all the accessible articles based on the inclusion and exclusion criteria and collected the relevant data of the studies.RESULTS:The animal models for sepsis are commonly induced through cecal ligation and puncture(CLP) or lipopolysaccharide(LPS) injection.SAE can be evaluated using nervous reflex scores and sepsis evaluation during the acute phase,or through Morris water maze(MWM),openfield test,fear condition(FC) test,inhibitory avoidance,and other tests during the late phase.CONCLUSION:CLP and LPS injection are the most common methods for establishing SAE animal models.Nervous reflexs cores,MWM,FC test,and inhibitory avoidance are widely used in SAE model analysis.Future research should focus on establishing a standardized system for SAE development and analysis.

Predictive value of systemic immunity index for sepsis in low-medium risk community-acquired pneumonia

Objective:To assess the predictive value of systemic immune inflammation index(SII)for sepsis in low-and medium-risk community-acquired pneumonia.Methods:A total of 589 elderly patients with low-and medium-risk community-acquired pneumonia admitted to the Emergency Department of the Second Affiliated Hospital of Hainan Medical University from January 2020 to January 2023 were included as the research subjects,and the general information and laboratory test results of the patients were collected,and the optimal cut-off value of continuous variables for predicting sepsis in elderly patients with low-and medium-risk community-acquired pneumonia was determined by plotting the receiver work characteristic(ROC)curve,which was converted into dichotomous variables and univariate and multivariate logistic Regression analysis of the influencing factors of sepsis in elderly patients with low-and medium-risk community-acquired pneumonia.Based on this,a nomogram model is constructed to predict the risk of sepsis.The differentiation,consistency and accuracy of the model were verified by calibration curve and subject operating characteristic(ROC)curve,and the clinical utility of the model was determined by decision curve analysis.Results:A total of 589 elderly patients with low-and intermediate-risk community-acquired pneumonia were included in this study,of which 96(16.30%)developed sepsis.There were significant differences in age,diabetes mellitus and chronic obstructive pulmonary disease,Lac,PCT,SII and other indexes between sepsis and non-sepsis groups(P<0.05).Logistics regression analysis showed that age,diabetes mellitus and chronic obstructive pulmonary disease,Lac,and SII were independent risk factors for sepsis in elderly patients with low-and medium-risk community-acquired pneumonia.The nomogram prediction model was used to verify the results,and the AUC was 0.826(95%CI:0.780-0.872),and the calibration curve tended to the ideal curve with good accuracy.The decision curve shows that when the threshold of the model is between 0.10~0.78,the model has the advantage of clinical benefit.Conclusion:The nomogram prediction model constructed based on SII to predict sepsis in elderly patients with low-and medium-risk community-acquired pneumonia has good accuracy,which can predict the occurrence of sepsis early,help early identification of high-risk groups and timely intervention,and thus improve the prognosis of patients.

Risk factors of concurrent urinary sepsis in patients with diabetes mellitus comorbid with upper urinary tract calculi

BACKGROUND Urinary sepsis is frequently seen in patients with diabetes mellitus(DM)complicated with upper urinary tract calculi(UUTCs).Currently,the known risk factors of urinary sepsis are not uniform.AIM To analyze the risk factors of concurrent urinary sepsis in patients with DM complicated with UUTCs by logistic regression.METHODS We retrospectively analyzed 384 patients with DM complicated with UUTCs treated in People’s Hospital of Jincheng between February 2018 and May 2022.The patients were screened according to the inclusion and exclusion criteria,and 204 patients were enrolled.The patients were assigned to an occurrence group(n=78)and a nonoccurrence group(n=126).Logistic regression was adopted to analyze the risk factors for urinary sepsis,and a risk prediction model was established.RESULTS Gender,age,history of lumbago and abdominal pain,operation time,urine leukocytes(U-LEU)and urine glucose(U-GLU)were independent risk factors for patients with concurrent urinary sepsis(P<0.05).Risk score=0.794×gender+0.941×age+0.901×history of lumbago and abdominal pain-1.071×operation time+1.972×U-LEU+1.541×U-GLU.The occurrence group had notably higher risk scores than the nonoccurrence group(P<0.0001).The area under the curve of risk score for forecasting concurrent urinary sepsis in patients was 0.801,with specificity of 73.07%,sensitivity of 79.36%and Youden index of 52.44%.CONCLUSION Sex,age,history of lumbar and abdominal pain,operation time,ULEU and UGLU are independent risk factors for urogenic sepsis in diabetic patients with UUTC.

Current Problems of the Diagnostics and Treatment of Sepsis and Burn Injuries: The Modified Pathogenetic Concept

Background: The deep understanding of pathogenesis is a key moment in the formation of the modern strategy of modern medicine. We conducted the thorough analysis of the microscopic processes occurring in the bodies of patients with purulent-septic complications. The modified pathogenetic concept of the diagnostic and treatment model of diseases with septic complications is presented. The obtained information about the mechanisms of origin and development of these diseases is fundamentally important for finding the modern effective methods of treating patients. The aim of the research is to modify treatment tactics for patients with sepsis and burn injuries based on the modified pathogenetic concept using modern diagnostics, i.e. the method of fluorescence spectroscopy (MFS) and biomarkers. Materials and Methods: The proposed modified pathogenetic concept of the diagnostic and treatment model of diseases with purulent-septic complications along with standard methods was used successfully for effective treatment of 15 patients with sepsis and 25 with burn injuries. Results: 3 main scenarios of behaviour of spectral-fluorescence characteristics of patients with sepsis are illustrated. Spectral-fluorescence markers of sepsis were studied, which are informative 24 to 48 hours before the appearance of obvious clinical and laboratory signs of significant changes in the general somatic status of patients. Conclusions: The proposed diagnostic and therapeutic approach is new and fundamentally important for diagnostics and monitoring of the process of treatment of patients with purulent-septic diseases and burn injuries. An in-depth understanding of the dynamics of septic complications and the corresponding changes of the main markers of these diseases during treatment is especially relevant. The use of infusion therapy with solutions of donor albumin as an effective pathogenetic treatment is scientifically justified.

Predictive value of controlling nutritional status score for progression to chronic critical illness in elderly patients with sepsis

Objective:To investigate the predictive value of controlling nutritional status(CONUT)score for progression to chronic critical illness sepsis in elderly patients,and to construct a predictive model based on CONUT score histogram.Methods:739 elderly patients with sepsis admitted from January 2020 to December 2022 were selected as the study objects,and were divided into chronic critical illness group(n=188)and non-chronic critical illness group(n=551)according to whether chronic critical illness disease occurred.Clinical data of the patients were collected and compared.The predictive value of CONUT score,PNI and NLR in the progression of senile sepsis to chronic severe disease was compared,and the optimal threshold value was determined,which was used to convert the numerical variables into binary variables.Through univariate analysis and multivariate Logistic regression analysis,the risk factors affecting the progression of elderly sepsis patients to chronic critical illness disease were screened out,and the prediction model was built based on the nomogram.The efficacy and clinical utility of the prediction model were evaluated by the area under the ROC curve(AUC),calibration curve and decision curve analysis(DCA).Results:The best cut-off value for CONUT score in predicting elderly sepsis progressing to chronic critical illness was 4 points.The predictive performance of CONUT score(AUC=0.739)was better than that of PNI(AUC=0.609)and NLR(AUC=0.582)in elderly sepsis progressing to chronic critical illness(CONUT score vs PNI:Z=5.960,P<0.001;CONUT score vs NLR:Z=6.119,P<0.001).Univariate analysis showed that age,CCI score,SOFA score,sepsis shock,serum Lac,CONUT score,mechanical ventilation(MV),and continuous renal replacement therapy(CRRT)treatment were related to elderly sepsis progressing to chronic critical illness(P<0.05).Multivariate logistic regression analysis showed that CONUT score≥4 points,age≥75 years,CCI score≥3 points,SOFA score>5 points,sepsis shock,and serum Lac≥4 mmol/L were independent risk factors for elderly sepsis progressing to chronic critical illness(P<0.05).The nomogram showed that CONUT score had the greatest contribution value in predicting elderly sepsis progressing to chronic critical illness.Based on this,the nomogram prediction model had an AUC of 0.846[95%CI(0.812~0.879)],with a sensitivity of 75.5%and specificity of 81.3%,indicating good predictive performance.The calibration curve was close to the ideal curve,and the DCA threshold had clinical utility advantages when ranging from 0.1 to 0.9.Conclusion:The nomographic prediction model based on CONUT score can effectively predict the risk probability of senile sepsis progressing to chronic critical illness,helpful for clinicians to identify the high risk group of chronic and severe senile sepsis,which is helpful for clinicians to identify high-risk populations of elderly sepsis with chronic critical illness.

Experimental models of high-risk bowel anastomosis in rats:A systematic review

BACKGROUND Anastomotic leaks remain one of the most dreaded complications in gastrointestinal surgery causing significant morbidity,that negatively affect the patients’quality of life.Experimental studies play an important role in understanding the pathophysiological background of anastomotic healing and there are still many fields that require further investigation.Knowledge drawn from these studies can lead to interventions or techniques that can reduce the risk of anastomotic leak in patients with high-risk features.Despite the advances in experimental protocols and techniques,designing a high-quality study is still challenging for the investigators as there is a plethora of different models used.AIM To review current state of the art for experimental protocols in high-risk anastomosis in rats.METHODS This systematic review was performed according to The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.To identify eligible studies,a comprehensive literature search was performed in the electronic databases PubMed(MEDLINE)and Scopus,covering the period from conception until 18 October 2023.RESULTS From our search strategy 102 studies were included and were categorized based on the mechanism used to create a high-risk anastomosis.Methods of assessing anastomotic healing were extracted and were individually appraised.CONCLUSION Anastomotic healing studies have evolved over the last decades,but the findings are yet to be translated into human studies.There is a need for high-quality,well-designed studies that will help to the better understanding of the pathophysiology of anastomotic healing and the effects of various interventions.

Comparison of Different Modes of Molding in Canine Sepsis

Sepsis can cause a series of damages to various organs of the body,so it has always been regarded as a hot research topic in veterinary clinic.Aiming at the present situation of high morbidity and mortality of canine sepsis,in order to further explore the pathogenesis of this disease,it need to establish a stable and repeatable canine sepsis model that is in line with the clinical characteristics of the disease.The study selected 12 local dogs and randomly divided into three groups:rapid bolus injection group(Group A),continuous infusion group within 30 min(Group B)and continuous infusion group(Group C).Then,the lipopolysaccharides(LPS)with 2 mg·kg^-1 were injected through the brachial vein in different modes of administration,thus the model was fully established.During the modeling period,body temperature(T),respiratory rate(RR),heart rate(HR)and mean arterial pressure(MAP)were monitored at 0,10,20,30,40,50 min and 1,2,3,4,5,6,7,8,9,12 and 24 h.Blood was collected from the canine brachial vein at 0,1,2,3,4,5,6,7,8,9,12 and 24 h,respectively,for the detection of white blood cells(WBC).The test showed that the values of T,RR,HR,MAP,WBC of the dogs in group A all changed but did not exceed the normal range,and the clinical symptoms were not significant.There were no significant changes in the values of RR,HR,T,MAP and WBC of the dogs in Group B,and the clinical symptoms were not significant.The value of T of the dogs in Group C were significantly increased at 40 min(p<0.05),which reached the fever standard and lasted for 7 h;the value of RR increased significantly at 20 min(p<0.05),and a downward trend could be observed at 12 h,then it returned to normal at 24 h;the value of HR increased significantly at 50 min(p<0.05)and recovered at 8 h;the value of HR decreased significantly at 20 min(p<0.05),which remained at 12 h(p<0.05),and returned back to normal at 24 h;the value of WBC decreased significantly from 1 h to 4 h(p<0.05),which was lower than the normal value,and increased significantly at 24 h(p<0.01);all of the four dogs in this group had clinical symptoms such as vomiting,diarrhea and depression.Based on the above results,the changes of indexes and clinical symptoms in Groups A and B did not meet the standards of sepsis.After a long-term continuous intravenous infusion of LPS,the experimental dogs in Group C showed varying degrees of clinical symptoms,such as vomiting,diarrhea and depression one after another.The indexes and clinical symptoms reached the sepsis standard about 3 h after infusion.In brief,this model not only had good stability and good regularity of repeatability,but also lasted for a long time and could be suitable for other subsequent studies.

Short term protective effect of digitoxin in sepsis-induced acute lung injury

Purpose:Digitoxin is a cardiac glycoside used in the treatment of heart failure.Inspired by its known antiinflammatory effect,this study aims to investigate the effect of digoxin in a sepsis model and to bring to light its effect and underlying mechanism in acute lung injury(ALI).Method:28 wistar albino rats were divided into 4 groups.Sepsis model is performed by the feces intraperitoneal-injection procedure(FIP).Results:TNF-a,CRP,IL-6,IL 1-Beta,lactic acid,and MDA values were significantly decreased in the FIP+digitoxin group compared to the FIP+Saline group.When the same groups were examined,histological improvements such as decrease in alveolar inflammation and decrease in septal thickening in the digitoxin group and thorax CT were found to be significantly higher in the Hounsfield unit digitoxin group compared to the Saline group.Conclusion:Digitoxin has shown biochemical improvement in sepsis with all known mechanisms of action,and healing effects in both computerized tomography and histology in the lung.

瑞香素调节STING/TBK1/IRF3信号通路对脓毒症大鼠免疫炎症反应的影响

目的探究瑞香素调节STING/TBK1/IRF3信号通路对脓毒症大鼠免疫炎症反应的影响。方法选用80只雄性Sprague Dawley(SD)大鼠,将大鼠随机分为4组,假手术组20只;其余60只按照盲肠结扎穿刺法(CLP)构建脓毒症小鼠模型,腹腔注射不同剂量瑞香素,分为无瑞香素模型组(0 mg/kg)、低剂量组(2.5 mg/kg)、高剂量组(5 mg/kg),每组20只;模型组及假手术组腹腔注射等量0.1%DMSO。观察CLP建模后的各组大鼠存活率。收集肺、肾、肝和脾组织进行病理组织学分析。ELISA检测大鼠血清炎症因子(TNF-α、IL-6、IL-1β),流式细胞术检测外周血中的T淋巴细胞亚群,Western blotting检测STING/TBK1/IRF3信号通路蛋白表达变化。结果与假手术组相比,模型组大鼠生存率降低(P<0.05),各个脏器组织损伤明显,血清炎症因子(TNF-α、IL-6、IL-1β)水平上升(P<0.05),外周血CD4^(+)比例、CD4^(+)/CD8^(+)比值均降低(P<0.05),CD8^(+)比例、Th1/Th2比值均升高(P<0.05),STING、p-TBK1/TBK1、p-IRF3/IRF3蛋白表达均下调(P<0.05)。与模型组相比,瑞香素高剂量组提高了大鼠生存率(P<0.05),各脏器组织损伤明显减轻,血清炎症因子水平降低(P<0.05),外周血CD4^(+)比例、CD4^(+)/CD8^(+)比值升高(P<0.05),CD8^(+)比例、Th1/Th2比值降低(P<0.05),STING、p-TBK1/TBK1、p-IRF3/IRF3蛋白表达升高(P<0.05)。结论瑞香素可通过调节STING/TBK1/IRF3信号通路,改善脓毒症大鼠免疫炎症反应。

基于MIMIC-Ⅳ数据库的脓毒性心肌病风险预测模型构建与评价

目的分析脓毒性心肌病(SC)的危险因素,构建与评价SC风险预测模型。方法从MIMIC-Ⅳ数据库中提取脓毒症患者的临床数据,按7∶3比例随机分为训练集和验证集。根据是否患有SC,分为SC组和非SC组。通过单因素和多因素Logistic回归分析筛选SC的独立危险因素,构建风险预测模型,并绘制列线图。采用受试者工作特征曲线下面积(AUC)评估模型的区分度,校正曲线评估模型的校准度,决策曲线分析(DCA)评估模型的临床适用度。结果共纳入2628例脓毒症患者,其中训练集1865例,验证集763例。训练集和验证集SC发病率差异无统计学意义(58.98%比62.25%,P=0.120)。除慢性阻塞性肺疾病(P=0.015)和重症监护室住院时长(P=0.016),其余临床指标两组间差异均无统计学意义(P均>0.05)。Logistic回归分析结果显示,既往患有冠心病(P=0.028)、心力衰竭(P<0.001)、中性粒细胞计数升高(P=0.001)、淋巴细胞计数降低(P=0.036)、肌酸激酶同工酶升高(P<0.001)、尿素氮升高(P=0.042)是SC的独立危险因素。训练集列线图预测模型的AUC为0.759(95%CI=0.732~0.785),验证集列线图预测模型的AUC为0.765(95%CI=0.723~0.807);两个数据集拟合度较好(训练集P=0.075,验证集P=0.067);DCA结果显示列线图预测模型具有良好的临床适用度。结论基于基础疾病及临床生化指标构建的列线图预测模型能够较好地预测SC的发生风险。

脓毒症患者并发急性肾损伤的危险因素分析及Nomogram预测模型的构建

目的分析脓毒症患者并发急性肾损伤的危险因素,并构建列线图(Nomogram)预测模型。方法选取2020年3月至2022年9月就诊的180例脓毒症患者为研究对象,根据患者是否并发急性肾损伤将其分为急性肾损伤组(n=75)和非急性肾损伤组(n=105)。采用受试者工作特征(ROC)曲线分析连续性变量的预测价值;采用logistic回归分析影响脓毒症患者并发急性肾损伤的危险因素;采用内部数据验证Nomogram模型临床效能。结果两组患者在年龄等一般资料的比较中,差异无统计学意义(P>0.05)。与非急性肾损伤组相比,急性肾损伤组患者男性较多,肺部感染者较多,平均动脉压(MAP)、前降钙素水平较低,乳酸、白细胞计数、多器官功能衰竭(MODS)评分水平较高(P<0.05)。MAP、乳酸、前降钙素、白细胞计数、MODS评分的ROC曲线下面积(AUC)为0.823、0.921、0.663、0.948、0.946,最佳截断值为89 mmHg、2.13 mmol/L、13.22μg/L、15×10^(9)·L^(-1)、6分。性别(男)、肺部感染(是)、MAP(≤89 mmHg)、乳酸(>2.13 mmol/L)、白细胞计数(>15×10^(9)·L^(-1))、MODS评分(>6分)均为影响脓毒症患者并发急性肾损伤的危险因素(P<0.05)。内部验证结果显示,Nomogram模型预测脓毒症患者并发急性肾损伤的风险C-index为0.763(95%CI:0.651~0.832);模型预测脓毒症患者并发急性肾损伤的风险阈值>0.07,Nomogram模型提供临床净收益。结论性别(男)、肺部感染(是)、MAP(≤89 mmHg)、乳酸(>2.13 mmol/L)、白细胞计数(>15×10^(9)·L^(-1))、MODS评分(>6分)均为影响脓毒症患者并发急性肾损伤的危险因素,且基于以上变量构建的Nomogram模型可以对患者并发急性肾损伤进行较好的预测。

个体化预测脓毒血症患儿并发急性肾损伤列线图模型的建立及验证

目的构建及验证脓毒血症患儿并发急性肾损伤(AKI)的列线图预测模型,并进行验证。方法本研究设计为回顾性研究,收集2019年8月至2021年8月在我院治疗的108例脓毒症患儿的临床资料。通过单因素和多因素Logistic回归分析脓毒血症患儿并发AKI的独立危险因素,利用R软件(R 4.0.3)构建列线图模型,采用Bootstrap法进行内部验证,采用校正曲线、Hosmer-Lemeshow检验和ROC曲线评价模型的预测能力。结果108例脓毒症患儿中,30例(27.78%)并发AKI(AKI组),78例(72.22%)无发生AKI(无AKI组)。AKI组与无AKI组的机械通气时间、急性生理与慢性健康评分(APACHEⅡ评分)、降钙素原(PCT)、C-反应蛋白(CRP)、白蛋白(ALB)、肌酸激酶(CK)等比较,差异均有统计学意义(均P<0.05)。多因素Logistic回归分析显示,机械通气时间(OR=1.245,95%CI:1.004~1.545)、APACHEⅡ评分(OR=1.529,95%CI:1.068~2.187)、PCT(OR=1.597,95%CI:1.237~2.061)、CRP(OR=1.046,95%CI:1.012~1.080)、ALB(OR=0.815,95%CI:0.721~0.979)、CK(OR=0.814,95%CI:0.730~0.942)是脓毒血症患儿并发AKI的独立影响因素(P<0.05)。基于上述影响因素建立列线图预测模型,经内部验证,校准曲线的平均绝对误差(MAE)为0.031,预测值与实际值基本一致;Hosmer-Lemeshow拟合优度检验显示模型拟合度较好(χ2=2.134,P=0.976)。曲线下面积(AUC)为0.965(95%CI:0.932~0.996),灵敏度为0.867,特异度为0.949。结论机械通气时间、APACHEⅡ评分、PCT、CRP、ALB、CK是脓毒血症患儿并发AKI的独立影响因素,基于上述因素建立的脓毒血症患儿并发AKI列线图预测模型具有良好的校准度和区分度,可为临床早期筛查脓毒血症并发AKI的高风险患儿及个体化干预方案的制定提供参考依据。

严重多发外伤患者并发脓毒症的危险因素及风险预测模型构建

目的分析严重多发外伤患者并发脓毒症的危险因素,并建立风险预测模型。方法收集南阳市第一人民医院2021年1月至2022年12月收治的120例严重多发外伤患者临床资料进行回顾性分析,依据是否并发脓毒症分为脓毒症组41例与非脓毒症组79例。采用logistic回归分析影响严重多发外伤患者并发脓毒症的危险因素,依据回归分析结果构建风险预测模型,并计算一致性指数(C-index)判断模型区分度。结果脓毒症组年龄、中性粒细胞与淋巴细胞计数比值(NLR)、活化部分凝血活酶时间(APTT)、创伤严重程度评分(ISS)、序贯器官衰竭(SOFA)评分均大于非脓毒症组,机械通气患者占比高于非脓毒症组,差异有统计学意义(P<0.05);经logistic回归分析显示,NLR、APTT、ISS评分为严重多发外伤患者并发脓毒症的独立危险因素(OR>1,P<0.05);绘制列线图构建严重多发外伤患者并发脓毒症的风险预测模型,验证模型区分度显示C-index值=0.908,区分度良好;绘制标准曲线显示,校准曲线和Y-X直线紧密贴合,模型准确度良好。结论NLR、APTT、ISS评分为严重多发外伤患者并发脓毒症的危险因素,基于上述因素构建的风险预测模型对严重多发外伤患者并发脓毒症具有较高预测价值。

脓毒症后综合征患者症状特征的潜在类别分析

目的探讨脓毒症后综合征患者症状的潜在类别,并分析不同潜在类别的影响因素。方法采用便利抽样方法,选取2021年1月-7月在福建省某三级甲等综合医院出院的脓毒症患者,患者出院后第3个月通过门诊及电话、微信视频相结合的方式进行问卷调查。对脓毒症后综合征患者的症状特征进行潜在类别分析,并通过单因素分析和多项分类Logistic回归识别其潜在类别的影响因素。结果共纳入347例脓毒症出院患者,其中216例(62.25%)发生脓毒症后综合征,出院后3个月认知障碍发生率为67.12%,焦虑发生率为61.57%,抑郁发生率为51.78%,睡眠障碍发生率为78.70%,日常生活能力障碍发生率为56.48%;脓毒症后综合征患者症状特征分别为“高症状组”(占比25.93%)、“认知要日常生活能力障碍组”(占比32.87%)和“睡眠障碍组”(占比41.20%);有既往史、使用镇痛药物越多归于“高症状组”的概率越大,APACHE域评分越高归于“高症状组”与“认知要日常生活能力障碍组”的概率越大,社会支持水平越高的归于“高症状组”与“认知要日常生活能力障碍组”的概率越小,激素药物使用越多归于“睡眠障碍组”的概率越小。结论脓毒症后综合征患者症状特征可分为“高症状组”“认知要日常生活能力障碍组”“睡眠障碍组”3个潜在类别,既往史、镇痛药物及激素使用、APACHE域评分、社会支持等因素在各潜在类别中存在异质性,可以预测各症状潜在类别的归属。

心导管留置术后盲肠结扎穿孔术(CLP)脓毒症动物模型的建立

目的采用留置心导管采血法检测盲肠穿孔术(CLP)后脓毒症模型大鼠血清学指标并观察肝肺组织病理学形态的变化,为用于治疗脓毒症药物的活性评价的动物模型的建立奠定了实验基础。方法采用改良的心导管留置术结合盲肠结扎穿孔术(CLP)建立脓毒症大鼠模型,术前和术后2、6、12、24、48 h共6个时相点采血,动态浊度法鲎试验检测血浆内毒素(LPS)水平,ELISA法检测血浆TNF-α和IL-6值,全自动血细胞分析仪检测全血白细胞(WBC)及血小板(PLT)值,术后48 h观察大鼠肝、肠、肺的病理学形态改变。结果术后大鼠的血浆LPS、TNF-α、IL-6及全血WBC水平均于术后6 h后逐渐升高,12 h达到高峰,之后逐渐下降,于48 h达到正常水平;PLT水平6 h内无明显变化,随后逐渐下降,24 h达最低值,之后逐渐升高,于48 h接近正常水平;肝、肠、肺组织则呈现以肿胀、炎性细胞浸润为主的病理学改变。结论通过心导管留置术采血观察CLP模型大鼠血细胞和细胞因子、LPS的动态变化是一稳定可靠的实验方法。

基于列线图模型分析老年重症脓毒症患者谵妄发生的风险因素

目的 基于列线图模型分析老年重症脓毒症患者谵妄发生的风险因素。方法 回顾性分析2021年10月-2023年10月新疆维吾尔自治区人民医院收治的308例老年重症脓毒症患者的临床资料,通过重症监护意识模糊评估法(CAM-ICU)评估患者是否发生谵妄,根据评估结果将患者分为谵妄组(103例)与非谵妄组(205例)。收集两组患者性别、年龄、受教育程度、基础疾病(高血压、高脂血症、冠心病、高血糖)、感染程度(严重脓毒症、脓毒症休克)、并发症(低氧血症、低蛋白血症、高碳酸血症、急性肾损伤、急性呼吸窘迫综合征)、是否使用镇静剂、基本生化指标等信息,并比较两组患者的序贯器官衰竭评估(SOFA)评分、炎症因子水平[C反应蛋白(CRP)、白细胞介素-6(IL-6)、降钙素原(PCT)]、可溶性蛋白-100β(S-100β)和同型半胱氨酸(Hcy)水平。采用多因素一般Logistic回归模型分析筛选患者发生谵妄的风险因素,构建列线图预测模型,并评价模型的拟合效果。结果 谵妄组年龄、SOFA评分、白细胞计数、CRP、IL-6、PCT、S-100β、Hcy水平均高于非谵妄组(P <0.05),血红蛋白水平低于非谵妄组(P <0.05);谵妄组中脓毒症休克、合并高血糖、并发低氧血症、低蛋白血症和高碳酸血症、使用镇静剂和机械通气的占比更高(P <0.05)。谵妄组与非谵妄组在性别构成、BIM、吸烟、酗酒、高血压、高脂血症、冠心病、急性肾损伤、急性呼吸窘迫综合征、机械通气、连续肾脏替代、淋巴细胞计数及肌酐水平方面比较,差异均无统计学意义(P>0.05)。多因素一般Logistic回归分析结果显示,年龄、脓毒症休克、高血糖、高碳酸血症、低蛋白血症、使用镇静剂、SOFA评分,以及IL-6、S-100β、Hcy水平均是影响重症老年脓毒症患者发生谵妄的重要因素(P <0.05)。校准曲线显示,此预测模型预测的校正曲线趋近于理想曲,曲线的平均绝对误差为0.029,敏感性为79.6%(95%CI:0.705,0.869),特异性为93.2%(95%CI:0.888,0.962),约登指数为0.718,曲线下面积为0.932(95%CI:0.904,0.960)。结论 重症老年脓毒症患者谵妄的发生与年龄、血糖、营养状况、疾病严重程度、治疗方式、炎症水平等多种因素有关,针对这些指标的评估有助于早期识别谵妄。

体感交互技术支持的“CLP模式”研究——以“运动障碍评估与训练”课程为例

为解决目前课程教学中面临的师资缺乏、理论课及实验课教学资源匮乏、实践课开展困难等问题,文章从虚拟现实技术、体感交互技术与教育康复教学的关系阐述出发,构建了体感交互技术支持的"CLP模式"。该模式由C—在线课堂、L—虚拟实验室、P—智慧实践基地三个核心部件组成,具有多重特色。最后,文章以"运动障碍评估与训练"课程为例,对"CLP模式"在课程中的2个应用案例进行了解析。文章的研究表明,体感交互技术应用于运动障碍评估和训练已逐渐成为一种发展趋势。

析因设计评价盲肠结扎穿孔(CLP)脓毒症大鼠模型严重程度的影响因素

目的目的探究盲肠结扎穿孔(CLP)脓毒症大鼠模型严重程度的影响因素。方法以盲肠结扎比例、穿刺针型号、抗生素使用情况为研究因素,分别选择结扎比例25%、50%、75%三种结扎方式,12号、16号穿刺针两种型号,使用抗生素与未使用抗生素两种情况,按照3×2×2型析因实验设计方法将84大鼠按随机数字表法随机分为14组,每组6只,建立CLP大鼠模型,以大鼠生存率、24h肝脏IL-1α、TNF-α、IL-6细胞因子的相对表达量为研究因素,运用SPSS21.0统计软件包进行析因方差分析。结果随着盲肠结扎比例的增加,CLP脓毒症大鼠的死亡率上升,存活时间缩短,差异具有显著统计学意义(P<0.05),同时IL-1α、TNF-α、IL-6表达水平均值逐渐升高;析因方差分析显示三种固定因素中盲肠结扎比例在三种细胞因子表达水平的主效应具有显著统计学差异(P<0.05),穿刺针型号及抗生素使用情况的主效应无显著统计学意义(P>0.05),盲肠结扎比例与抗生素使用情况两因素具有交互作用(P<0.05)。结论盲肠结扎比例是CLP脓毒症大鼠模型死亡率及感染程度的重要决定因素,盲肠结扎比例与抗生素应用情况两因素间对细胞因子表达水平具有交互性作用。

机器学习在脓毒症诊治中应用研究进展

目前,机器学习在重症医学科发展迅速,脓毒症诊疗中的应用更是目前研究的热点。集成算法、决策树、神经网络等监督学习法在患者紧急入院时脓毒症早期诊断与风险评估中具有重要意义,但监督学习算法要求所有数据进行标记,具有困难性;聚类算法和数据降维一类半监督学算法在脓毒症预测、脓毒症预后因素分析等方面应用较为常见,但算法相对简单,在多分类任务的处理上得出结果不理想;半监督学习算法结合了前两者,在现实世界更为实用,鉴于半监督学习算法的数据特征,在脓毒症诊疗的决策支持应用方面有待统筹。作者从脓毒症预测及诊断中常见模型的角度总结不同机器学习模型在脓毒症预测及诊断中的应用并进行综述,以期为国内学者提供参考。

个体化预测脓毒症患者并发急性肾损伤的风险列线图的建立及验证

目的建立脓毒症患者发生急性肾损伤(acute kidney injury,AKI)的早期预测列线图模型及其验证。方法选取2020年1月~2021年12月兰州大学第二医院接收的162例脓毒症患者为建模组,选取2022年1~12月接收的93例脓毒症患者为验证组。将建模组患者分为脓毒症合并AKI组(n=52)和脓毒症未合并AKI组(n=110)。对建模组患者采用Logistic回归分析筛选影响脓毒症患者发生AKI的危险因素;采用R软件构建预测脓毒症患者发生AKI的列线图模型。结果脓毒症合并AKI组和脓毒症未合并AKI组机械通气、重症监护病房(intensive care unit,ICU)住院时间、降钙素原(procalcitonin,PCT)水平、白细胞介素-6(interleukin-6,IL-6)水平、肿瘤坏死因子-α(tumour necrosis factor-α,TNF-α)水平、血乳酸水平比较,差异均有统计学意义(P<0.05)。多因素Logistic回归分析结果显示,机械通气、ICU住院时间≥3天、高水平PCT、高血乳酸水平是脓毒症患者发生AKI的独立危险因素(P<0.05)。基于危险因素采用R软件建立列线图模型,建模组受试者工作特征(receiver operating characteristic,ROC)曲线下面积为0.830,验证组ROC曲线下面积为0.845;根据列线图模型的结果显示,校准曲线预测值与实际值之间基本相符。Hosmer-Lemeshow拟合优度检验结果表明,建模组χ^(2)=7.340,P=0.501;验证组χ^(2)=7.758,P=0.458。结论构建预测ICU脓毒症患者发生AKI的风险列线图模型具有较大临床价值,可在临床上用于指导个体化治疗。