Backgrounds:Sepsis is a leading cause of in-hospital mortality. However, its prevalence is increasing among the elderly population. Therefore, early identification and prediction of the risk of death in elderly patients with sepsis is crucial. The objective of this study was to create a machine learning model that can predict short-term mortality risk in elderly patients with severe sepsis in a clear and concise manner. Methods:Data was collected from the MIMIC-IV (2.2). It was randomly divided into a training set and a validation set using a 7:3 ratio. Mortality predictors were determined through Recursive Feature Elimination (RFE). A prediction model for 28 days of ICU stay was built using six machine-learning algorithms. To create a comprehensive and nuanced model resolution, Shapley Additive Explanations (SHAP) and Local Interpretable Model-Agnostic Explanations (LIME) were used to systematically interpret the models at both a global and detailed level. Results:The study involved the analysis of 4,056 elderly patients with sepsis. A feature recursive elimination algorithm was utilized to select eight variables out of 49 for model development. Six machine learning models were assessed, and the Extreme Gradient Boosting (XGBoost) model was found to perform the best. The validation set achieved an AUC of 0.88 (95% CI: 0.86-0.90) and an accuracy of 0.84 (95% CI: 0.81-0.86) for this model. To examine the roles of the eight key variables in the model, SHAP analysis was employed. The global ranking order was made evident, and through the use of LIME analysis, the weights of each feature range in the prediction model were determined. Conclusion:The study's machine learning prediction model is a dependable tool for forecasting the prognosis of elderly patients with severe sepsis.

ObjectiveThe objective of this study was to create and validate a clinical prediction model for the incidence of major adverse cardiovascular events (MACE) within one year after percutaneous coronary intervention (PCI) in elderly patients diagnosed with acute coronary syndromes (ACS)MethodsThe study will use 70% of the 738 patients for model training and the remaining 30% for model validation. The feature recursive elimination algorithm (RFE) and the least absolute shrinkage selection operator (LASSO) regression technique will be used to identify the best combination of features. We compare the clinical prediction model we constructed with GRACE in terms of discrimination, calibration, recall, and clinical impactResultsWe used the RFE and LASSO regression technique to select 8 key variables from 44 candidates for our predictive model. The predictive model was found to have a good fit based on the Hosmer-Lemeshow test results (χ2 = 6.245). Additionally, the Brier score of the clinical prediction model was 0.1502, confirming its accuracy. When comparing our clinical prediction model to the widely used GRACE scoring system, the results showed that our model had slightly better predictive efficacy for the dataset involved in this study. The NRI was 0.6166, NRI + was 0.2262, NRI- was 0.3904, and IDI was 0.1272, with a P value of <0.001. The validation set's AUC was 0.787, indicating the prediction model has high differentiation and discriminative ability.ConclusionThis model assists in the early identification of the risk of MACE within one year after PCI for ACS in elderly patients.

目的 探讨经颅超声联合经胸心脏声学造影(cTCCD+cTTE)技术在军事人员卵圆孔未闭(PFO)中的诊断价值.方法 以怀疑存在PFO 的军事人员作为研究对象,包括 16 例军事飞行人员和 8 例一般军事人员,分析cTCCD+cTTE判断PFO 有无、静息状态及 Valsalva动作下右向左分流(RLS)的情况,并对发现存在 RLS 的病例进一步行经食管超声心动图(TEE)检查.结果 5 例临床怀疑PFO 的军事飞行人员 cTCCD+cTTE检查为阴性;余 19 例(包括 11 例军事飞行人员及 8 例一般军事人员)cTCCD+cTTE法可见PFO-RLS,包括 8 例常规经胸超声心动图(TTE)检查判定为PFO 和 11 例常规TTE检查未检出PFO 的人员.未检出的 11 例PFO 人员中,TEE在 8 例中可见过隔血流,检出率为 72.7%.与 cTTE、cTCCD比较,cTCCD+ cTTE法在平静状态下检出率较两者均提高 15.8%,Valsalva动作下检出率分别提高了 5.3%和 10.5%,而且固有型比例及中大量分流检出率均有所提高.结论 TTE检查在PFO-RLS中灵敏度低,cTCCD+cTTE能够显著提高PFO-RLS的检出率;有效地执行 Valsalva动作在判断PFO-RLS中具有重要价值.

Myocardial infarction is still a leading cause of morbidity and mortality worldwide, but its pathogenesis has not been fully understood. In the study, we attempted to explore the effects of E3 ligase tripartite motif 16 (TRIM16) on myocardial ischemia-reperfusion (MI/R) injury in vivo and in vitro, and the underlying mechanisms. We identified that TRIM16 was indeed a potent regulator during MI/R progression in murine models and surprisingly showed a negative correlation with the concentrations of cardiac pro-inflammatory cytokines. Adenoviral vectors encoding GFP or TRIM16 (Ad-TRIM16) were subjected to mice through direct injection into the left ventricular (LV). We found that Ad-TRIM16 significantly reduced the infarct size, and improved the cardiac function and structure compared with the Ad-GFP mice after MI/R operation. More studies indicated that TRIM16 over-expression strongly meliorated nucleotide-binding oligomerization domain-like receptor family pyrin domain containing 3 (NLRP3) inflammasome and associated inflammatory response in hearts of MI/R-induced mice, which were validated in hypoxia/reoxygenation (H/R)-exposed primary cardiomyocytes in vitro. In particular, MI/R operation led to cardiac pyroptosis by increasing the cleavage of Caspase-1 and Gasdermin D (GSDMD), while being considerably abrogated upon TRIM16 over-expression. Mechanistically, TRIM16 interacted with NLRP3 and promoted the K48-linked polyubiquitination of NLRP3, ultimately promoted its degradation. Together, we identified TRIM16 as a novel E3 ubiquitin ligase for NLRP3, which played an essential role in modulating its expression, and subsequently influenced inflammatory response and pyroptosis in MI/R murine model, confirming that TRIM16 may be a potential therapeutic target for myocardial infarction.

目的 心肌细胞的自噬受到非常精细地调节，本实验探讨ω-3不饱和脂肪酸是否能通过影响自噬改善心肌细胞损伤并深入研究其机制。方法 使用H9C2细胞系以及成年C57BL/6小鼠心肌细胞原代培养，将心肌细胞暴露于血管紧张素Ⅱ和ω-3不饱和脂肪酸环境中，检测心肌细胞结构稳定性和心肌细胞自噬状态，检测指标包括心肌细胞骨架蛋白α-Actinin变化情况变化、细胞自噬流水平变化及细胞自噬相关蛋白变化等。结果 血管紧张素Ⅱ诱导心肌细胞中α-Actinin纤维排列消失，变为散点状结构。ω-3多不饱和脂肪酸使心肌细胞α-Actinin纤维排列结构保持正常。血管紧张素Ⅱ可诱导心肌细胞自噬流明显上调（P＜0.01），而ω-3多不饱和脂肪酸可抑制暴露于血管紧张素Ⅱ的H9c2细胞自噬水平（P＜0.01）。血管紧张素Ⅱ提升细胞LC3Ⅱ/LC3Ⅰ表达，而ω-3多不饱和脂肪酸能够抑制LC3Ⅱ/LC3Ⅰ水平的升高。结论 ω-3多不饱和脂肪酸可通过调节自噬水平来减轻心肌细胞的结构损伤。

BACKGROUND:Intestinal ischemia/reperfusion (I/R) injury is a fatal syndrome that occurs under many clinical scenarios. The apoptosis of intestinal cells caused by ischemia can cause cell damage and provoke systemic dysfunction during reperfusion. However, the mechanism of I/R-induced apoptosis remains unclear. Cystic fibrosis transmembrane conductance regulator (CFTR) is a cAMP-activated chloride channel. Few researchers have paid attention to its role in intestinal I/R injury, or the relationship between CFTR and intestinal apoptosis induced by hypoxia/reoxygenation (H/R).AIM:To investigate the effects of CFTR on I/R-induced intestinal apoptosis and its underlying molecular mechanisms.METHODS:An intestinal I/R injury model was established in mice with superior mesenteric artery occlusion, and Caco2 cells were subjected to H/R for the simulation of I/R in vivo.RESULTS:The results suggested that CFTR overexpression significantly increased the Caco2 cell viability and decreased cell apoptosis induced by the H/R. Interestingly, we found that the translocation of p65, an NF-κB member, from the cytoplasm to the nucleus after H/R treatment can be reversed by the overexpression of CFTR, the NF-κB P65 would return from the nucleus to the cytoplasm as determined by immunostaining. We also discovered that CFTR inhibited cell apoptosis in the H/R-treated cells, and this effect was significantly curbed by the NF-κB activator BA, AKT inhibitor GSK690693 and the PI3K inhibitor LY294002. Moreover, we demonstrated that CFTR overexpression could reverse the decreased PI3K/AKT expression induced by the I/R treatment in vivo or H/R treatment in vitro.CONCLUSION:The results of the present study indicate that the overexpression of CFTR protects Caco2 cells from H/R-induced apoptosis; furthermore, it also inhibits H/R-induced apoptosis through the PI3K/AKT/NF-κB signaling pathway in H/R-treated Caco2 cells and intestinal tissues.

High-mobility group box 1 (HMGB1) is released by necrotic cells and serves an important role in cardiovascular pathology. However, the effects of HMGB1 in cardiomyocyte hypertrophy remain unclear. Therefore, the aim of the present study was to investigate the potential role of HMGB1 in cardiomyocyte hypertrophy and the underlying mechanisms of its action. Neonatal mouse cardiomyocytes (NMCs) were co-cultured with recombinant HMGB1 (rHMGB1). Wortmannin was used to inhibit PI3K activity in cardiomyocytes. Subsequently, atrial natriuretic peptide (ANP), 14-3-3 and phosphorylated-Akt (p-Akt) protein levels were detected using western blot analysis. In addition, nuclear factor of activated T cells 3 (NFAT3) protein levels were measured by western blot analysis and observed in NMCs under a confocal microscope. The results revealed that rHMGB1 increased ANP and p-Akt, and decreased 14-3-3 eta protein levels. Furthermore, wortmannin abrogated the effects of rHMGB1 on ANP, 14-3-3 eta and p-Akt protein levels. In addition, rHMGB1 induced nuclear translocation of NFAT3, which was also inhibited by wortmannin pretreatment. The results of this study suggest that rHMGB1 induces cardiac hypertrophy by regulating the 14-3-3 eta/PI3K/Akt/NFAT3 signaling pathway.

It remains uncertain whether low‐level electrical stimulation (LL‐ES) of the ventricular ganglionated plexi (GP) improves heart function. This study investigated the anti‐arrhythmic and anti‐heart failure effects of LL‐ES of the aortic root ventricular GP (ARVGP).

目的 探讨褪黑素在高糖诱导的原代心肌细胞损伤中的作用,并明确SIRT1在其中的作用及其机制.方法 将原代心肌细胞分为对照组(Con组)、褪黑素对照组(Con+Mel组)、高糖组(HG组)、高糖+褪黑素组(HG+Mel组)和SIRT1抑制剂理组(HG+Mel+EX527组).采用Cell Counting Kit-8(CCK-8)试剂盒检测细胞活性,丙二醛(MDA)和超氧化物歧化酶(SOD)试剂盒检测细胞氧化应激水平,TUNEL染色检测细胞凋亡,免疫印迹检测SIRT1、Beclin1、Atg5、cleaved Caspase-3、Bax和Bcl-2蛋白表达水平.结果 与Con组相比,HG组原代心肌细胞活力减低,氧化应激水平升高,细胞凋亡水平增加,SIRT1表达下调(P<0.05).给予褪黑素干预后,与Con组相比,Con+Mel组SIRT1表达量增加(P<0.05),而两组间细胞活力、氧化应激水平和细胞凋亡水平无显著差异(P>0.05).与HG组相比,HG+Mel组原代心肌细胞SIRT1表达量提高(P<0.05),细胞活力增加(P<0.05),氧化应激水平和细胞凋亡水平下降(P<0.05).免疫印迹结果显示,与Con组相比,HG组原代心肌细胞自噬相关蛋白Beclin1和Atg5表达减低(P<0.05),Con+Mel组Beclin1和Atg5表达明显上升(P<0.05);与HG组相比,HG+Mel组Beclin1和Atg5表达上升(P<0.05).此外,给予SIRT1特异性抑制剂EX527干预后,相比于HG+Mel组,HG+Mel+EX527组细胞凋亡比率增加(P<0.05),凋亡蛋白cleaved Caspase-3和Bax上调(P<0.05),抗凋亡蛋白Bcl-2下调(P<0.05),细胞自噬蛋白Beclin1和Atg5表达减低(P<0.05).结论 褪黑素可能通过上调SIRT1信号增强细胞自噬,改善高糖诱导的原代心肌细胞损伤.

Aberrant proliferation and migration of vascular smooth muscle cells contributes to cardiovascular diseases (CVDs), including atherosclerosis. MicroRNA-223 (miR-223) protects against atherosclerotic CVDs. We investigated the contribution of miR-223 to platelet-derived growth factor-BB (PDGF-BB)-induced proliferation and migration of human aortic smooth muscle cells (HASMCs). We found that miR-223 was downregulated in PDGF-BB-treated HASMCs in a dose- and time-dependent manner, while nuclear factor of activated T cells 5 (NFAT5) was upregulated. Gain- and loss-of-function studies demonstrated that miR-223 treatment reduced PDGF-BB-induced HASMC proliferation and motility, whereas miR-223 inhibitor enhanced these processes. Moreover, NFAT5 was identified as a direct target of miR-223 in HASMC. The inhibitory effects of miR-223 on HASMC proliferation and migration were partly rescued by NFAT5 restoration. Overall, these findings suggest that miR-223 inhibits the PDGF-BB-induced proliferation and motility of HASMCs by targeting NFAT5 and that miR-223 and NFAT5 may be potential therapeutic targets for atherosclerosis.

医学院校开展荣誉教育的目的在于培养特殊的医学本科拔尖人才,荣誉教育的目标不仅仅在于出类拔萃知识能力的培养,更在于培养医学生成为崇尚荣誉的优秀者,医疗实践的领航者.但荣誉教育与医德教育密不可分,医德教育可有效预防“荣誉教育”的负效应.为防止“荣誉教育”内容成为“孤岛”,需创新“荣誉教育”与医德教育相融合的教育教学模式.首先把道德内涵全息性地融入“荣誉教育”活动中;其次建立以未来“岗位胜任力”为导向的“荣誉教育”教学体系.基于“荣誉教育”与医德教育的融合统一,构建与优化医学教育课程结构,让通识教育与医学专业教育相结合,知识传授与能力培养相结合,最终达到培养高尚医德、精湛医术的卓越医师人才之目的.

通过对医院临床管理模拟教学的适用性分析,归纳出几种模拟技术支持下临床实践模拟教学模式的创新范例,并对其教学模式的具体实施路径和保障措施进行了探究,以利提高医院临床实践管理模拟教学的质量.

随着医学教育大数据挖掘和学习分析技术、量化学习和信息推送技术等新信息技术的开发,为医学教育课程教学及管理决策的优化带来机遇.探究和推广大数据环境下医学教育课程教学模式的创新成果,将是推动医学信息化进程的必由之路.分析了大数据支持医学教育课程改革的关键技术:数据挖掘与学习分析技术、量化学习与信息推送技术、学习场景与导学方案设计技术,归纳出基于大数据支持的医学教育课程教学系列创新范式,并探讨了医学教育课程教学创新模式的实施策略与路径.

Cardiac hypertrophy is an independent predictor of cardiovascular morbidity and mortality. To identify the mechanisms by which simvastatin inhibits cardiac hypertrophy induced by pressure overload, we determined effects of simvastatin on 14-3-3 protein expression and autophagic activity. Simvastatin was administered intragastrically to Sprague-Dawley (SD) rats before abdominal aortic banding (AAB). Neonatal rat cardiomyocytes (NRCs) were treated with simvastatin before angiotensin II (AngII) stimulation. 14-3-3, LC3, and p62 protein levels were determined by western blot. Autophagy was also measured by the double-labeled red fluorescent protein-green fluorescent protein autophagy reporter system. Simvastatin alleviated excessive autophagy, characterized by a high LC3II/LC3I ratio and low level of p62, and blunted cardiac hypertrophy while increasing 14-3-3 protein expression in rats that had undergone AAB. In addition, it increased 14-3-3 expression and inhibited excessive autophagy in NRCs exposed to AngII. Our study demonstrated that simvastatin may inhibit excessive autophagy, increase 14-3-3 expression, and finally exert beneficial effects on cardioprotection against pressure overload.

Background/Aims: This study was developed to investigate a potential therapeutic method for myocardial ischemia/reperfusion injury involving the promotion of miR-24-3p expression. Methods: Microarray analysis was used to screen differentially expressed genes in a myocardial ischemia/reperfusion (I/R) injury mouse model. Gene set enrichment analysis was utilized to determine vital signaling pathways. Targeting verification was conducted with a luciferase reporter assay. Myocardial I/R injury was developed in mice, and the expression levels of RIPK1 and miR-24-3p were investigated by qRT-PCR and Western blot. Hemodynamic parameters and the activity of serum myocardial enzymes were measured to evaluate cardiac function. Infarct area was observed through HE and TTC staining. Myocardial cell apoptosis was examined by TUNEL staining and caspase-3 activity analysis. Results: RIPK1 was an upregulated mRNA found by microarray analysis and a verified target of the downregulated miRNA miR-24-3p. The upregulation of RIPK1 (1.8-fold) and the downregulation of miR-24-3p (0.3-fold) were confirmed in I/R mice. RIPK1 led to impaired cardiac function indexes, increased infarct area and cell apoptosis, while miR-24-3p could reverse the injury by regulating RIPK1. The TNF signaling pathway was proven to be involved in myocardial I/R injury through the detection of the dysregulation of related proteins. Conclusion: In conclusion, RIPK1 was upregulated and miR-24-3p was downregulated in a myocardial I/R injury mouse model. RIPK1 could aggravate myocardial I/R injury via the TNF signaling pathway, while miR-24-3p could suppress RIPK1 and therefore exert cardioprotective effects in myocardial I/R injury.

目的:研究内质网应激(endoplasmic reticulum stress,ERS)在二十碳五烯酸(eicosapentaenoic acid,EPA)抵抗棕榈酸(palimitate,PAL)诱导的心肌细胞凋亡中的作用.方法:将培养的心肌细胞随机分为对照组、PAL处理组、EPA+PAL组、毒胡萝卜素(thapsigargin) +EPA+PAL组、thapsigargin组及thapsigargin+EPA组.采用CCK-8检测细胞活力、Tunel染色检测细胞凋亡率、Western印迹检测葡萄糖调节蛋白78(glucose-regulated protein 78,GRP78)和钙网蛋白(calreticulin,CRT),以及ERS促凋亡蛋白C/EBP同源蛋白(C/EBP homologous protein,CHOP)、JNK和半胱氨酸天冬氨酸蛋白酶12(caspase-12)的表达.结果:与对照组比较,PAL处理可显著降低心肌细胞活力,促进细胞凋亡,激活ERS应激相关GRP78和CRT,以及ERS促凋亡蛋白CHOP,p-JNK及活化的caspase-12(cleaved caspase-12)的表达(P＜0.05).相比于PAL组,EPA+PAL预处理可使PAL诱导的心肌细胞活力显著升高,GRP78,CRT,CHOP,cleaved caspase-12及p-JNK蛋白表达明显降低(P＜0.05),且使细胞凋亡率由43.9％降低至24.07％(P＜0.05).添加ERS特异性激活剂thapsigargin激活ERS后,与EPA+PAL组相比,thapsigargin+EPA+PAL组ERS应激相关蛋白GRP78和CRT蛋白表达比率显著升高,ERS促凋亡蛋白CHOP,JNK及caspase-12上调,心肌细胞活力下降,凋亡率增加.此外,与对照组比较,单独添加thapsigargin激活ERS,显著降低细胞活性,促进细胞凋亡,而EPA+thapsigargin组却明显逆转了thapsigargin对心肌细胞的促凋亡效应.结论:EPA可有效抑制PAL诱导的大鼠心肌细胞凋亡,其保护机制可能与抑制PAL诱导的心肌细胞ERS激活,进而抑制caspase依赖的级联凋亡反应有关.

随着现代模拟技术的不断更新和应用领域的不断深入,为心血管学临床教学的创新带来生机,模拟技术作为一种新型医学教学辅助技术,创造出许多行之有效的教学方法和模式.文章通过对现代模拟技术特征及优势分析,归纳出几种前瞻性并适宜推广的心血管疾病教学创新模式,并探讨了相应的实施路径和保障机制.

教育大数据技术推动了医学通识教育教学质量评价中数据驱动决策的实现,为多方参与教育评价、实现发展性学生评估提供了良好的支持.文章通过对通识教育教学质量评价现状及大数据促进医学通识教育教学评价变革的分析,提出构建基于大数据医学通识教育教学质量评价的框架体系及实施路径.

目的 初步探讨内质网应激PERK-ATF4-CHOP通路在褪黑素抵抗血管紧张素Ⅱ(angiotensinⅡ,AngⅡ)诱导的心肌细胞肥厚中的作用.方法 将培养的心肌细胞随机分为对照组、AngⅡ处理组、褪黑素组.采用乳酸脱氢酶(lactate dehydrogenase,LDH)法检测细胞活性,原位切口末端标记法(TUNEL)检测细胞凋亡率,Western blot检测蛋白激酶R样内质网激酶(protein kinase r-like endoplasmic reticulum kinase,PERK)、活性转录因子(Activating Transcription Factor,ATF)4、C/EBP同源蛋白(C/EBP homologous protein,CHOP)的表达水平,实时荧光定量聚合酶链反应(quantitative real-time polymerase chain reaction,qRT-PCR)检测心肌肥厚相关标识物心房钠尿肽(atrial natriuretic peptide,ANP)、脑钠尿肽(brain natriuretic peptide,BNP)和心肌β-肌球蛋白重链(β-myosin heavy chain,β-MHC) mRNA 表达量的变化;免疫荧光检测心肌细胞横截面积.结果 与对照组相比,AngⅡ能够刺激心肌细胞上调ANP、BNP和β-MHC表达(P＜0.05),刺激LDH释放(P＜0.05)、增加细胞凋亡比率和心肌细胞横截面积(P＜0.05);与AngⅡ组相比,褪黑素可以浓度依赖性显著抑制AngⅡ诱导的ANP、BNP和β-MHC的上调和LDH的积累,抑制心肌细胞的横截面积增加,降低细胞凋亡,并抑制诱导的PERK-ATF4-CHOP通路的激活(P＜0.05);与对照组相比,AngⅡ显著增加PERK、ATF4和CHOP的表达水平(P＜0.05),但给予褪黑素后,激活的PERK-ATF4-CHOP则被明显抑制(P＜0.05).结论 褪黑素可能通过抑制内质网应激PERK-ATF4-CHOP信号通路激活,改善AngⅡ诱导的乳鼠心肌细胞肥厚,为未来褪黑素的进一步临床研究拓展新思路.

Sepsis is a seriously critical ill and threat to the lives of children caused by infection,the clinical treatment is difficult.In recent years,the clinical monitoring and diagnosis and treatment strategies are under in-depth discussions.This paper mainly review the the diagnosis and treatment of myocardial injury in children through hemodynamic monitoring with ECG,cardiac biomarkers to monitor the combination treatment strategy of bundling and combining individual perspectives of pus thyrotoxicosis.