Understanding heart failure: pathophysiology and approach to therapy

Heart failure during childhood is a final common pathway resulting from a range of causes. Diagnosis and management are challenging, and the evidence base for therapy is significantly smaller than in the adult literature. Where evidence is lacking, understanding of the underlying pathology is helpful to determine which treatment strategies are likely to bring most benefit. The clinical and haemodynamic features of heart failure arise from both the initial insult and the subsequent neurohormonal response, which, although beneficial in the short-term, is ultimately deleterious. Initial optimal management is focused on determining the aetiology and then achieving haemodynamic stability along with euvolaemia. Subsequent management includes specific treatment of the underlying aetiology if remediable, as well as arresting the maladaptive neurohormonal cascade. Additional goals include facilitation of adequate growth and development, and provision of psycho-social support for the patient and their family. Although pharmacologic management is relatively unchanged in recent years, a few new agents have shown promise for improved outcomes. Mechanical support options continue to evolve, although challenges remain, particularly in small infants. For children with severe heart failure without a reversible aetiology and recalcitrant to pharmacologic therapy, transplantation provides good quality of life. However, although outcomes continue to improve, it does not offer normal life expectancy. A multi-disciplinary approach, and effective communication, remain key in caring for these complex children and their families. This short review gives an overview of current practice highlighting the principles which underpin management for children with heart failure.     

Molecular mechanism of reproductive toxicity induced by Tripterygium Wilfordii based on network pharmacology

To explore the possible molecular mechanism of reproductive toxicity of Tripterygium wilfordii from the perspective of network pharmacology and bioinformatics.The compounds of T wilfordii were obtained by querying the relevant Chinese medicine database, the effective compounds were screened and the corresponding targets were obtained, and then compared with the reproductive toxicities related to disease targets obtained from the disease gene database to infer the potential toxic targets of reproductive toxicity of T wilfordii. Then, the key targets of reproductive toxicity of T wilfordii were screened using Search Tool for the Retrieval of Interacting Genes/Protein and Cytoscape. The gene ontology function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, as well as module analysis, were performed on the key targets using Database for Annotation, Visualization, and Integrated Discovery and Cytoscape, respectively. Finally, the network between effective compounds-toxic targets was conducted to see how the compounds interacted.A total of 48 effective compounds and 482 potential toxic targets related to the reproductive toxicity of T wilfordii were screened. The enrichment analysis results showed that the key targets were mainly enriched in biological processes such as response to drug, ionotropic glutamate receptor signaling pathway, and KEGG pathways such as neuroactive ligand-receptor interaction, cAMP signaling pathway. In the protein-protein interaction network of potential toxic targets, there were 78 key targets such as TP53, INS, IL6, AGT, ADCY3, and so on. Enrichment analysis of the top module with 19 genes from module analysis indicated that T wilfordii might cause reproductive toxicity by gene ontology terms and KEGG pathways such as regulation of vasoconstriction, G-protein coupled receptor signaling pathway, inflammatory response, cAMP signaling pathway, and so on. In the network between effective compounds of T wilfordii and key targets, there were 5 compounds with high degree including Tingenone, Wilfordic Acid, Abruslactone A, Nobilin, and Wilforlide B.The complex molecular mechanism of reproductive toxicity of T wilfordii can be preliminarily elucidated with the help of the network pharmacology method, and the analysis results can provide some reference for the further mechanism research of reproductive toxicity of T wilfordii.     

不同分娩体位对枕后位/枕横位产妇母婴结局影响的网状Meta分析

目的 采用网状Meta分析方法,评价不同分娩体位对枕后位/枕横位产妇母婴结局的影响。 方法 计算机检索Cochrane Library、PubMed、Web of Science、Embase、CINAHL、中国生物医学文献数据库、中国知网、维普数据库中关于不同分娩体位对枕后位/枕横位产妇分娩结局影响的随机对照试验。经过文献筛选、质量评价、信息提取后,使用R4.1.1软件和Stata16.0软件进行网状Meta分析。 结果 本研究共纳入24篇文献,涉及12种体位,包含4 887名产妇。网状Meta分析结果显示,同侧侧俯卧位与自由体位比较,在胎头旋转为枕前位方面差异具有显著差异（RR=0.45,95%CI为0.22~0.88）;同侧卧位与截石位比较,在阴道分娩方面差异具有显著差异（RR=0.55,95%CI为0.30~0.97）。根据累积排序概率曲线下面积排序结果,同侧卧位、同侧侧俯卧位是改善枕后位/枕横位产妇分娩结局的较优体位。 结论 基于网状Meta分析和排序结果,同侧卧位和同侧侧俯卧位在改善枕后位/枕横位产妇分娩结局效果较好,但还需高质量、大样本的随机对照试验进一步验证。     

洗腿又方治疗骨关节炎的网络药理学研究

目的 通过生物信息学、网络药理学和分子对接探讨洗腿又方治疗骨关节炎的药理学机制。方法 从基因表达综合数据库(GEO)中获取骨关节炎滑膜的差异表达基因,使用TCMSP、HERB、TCMID等数据库搜集洗腿又方的活性成分及其作用靶点,并与疾病靶点取交集。通过STRING数据库及Cytoscape3.8.2软件对交集靶点进行蛋白互作和富集分析,最终将关键活性成分与关键靶点进行分子对接。结果 获得骨关节炎滑膜的差异表达基因2072个,洗腿又方的活性成分20种,其治疗骨关节炎的靶点30个,进一步通过蛋白互作筛选获得HIF1A、CASP8、RAF1等关键靶点,富集分析发现洗腿又方主要通过干预细胞周期、炎症和内分泌等信号通路治疗骨关节炎,分子对接结果显示,关键有效成分芹黄素、槲皮素分别与关键靶点HIF1A、CASP8有良好的对接活性。结论 本研究探讨了洗腿又方治疗骨关节炎的可能活性成分、靶点及作用通路,为其应用于骨关节炎的治疗提供了理论依据。     

基于网络药理学探讨祛痹痛风饮治疗痛风的作用机制

目的运用网络药理学方法探讨祛痹痛风饮治疗痛风的活性成分、作用靶点及其潜在的治疗作用机制。方法基于中药系统药理学数据库与分析平台(TCMSP)获取祛痹痛风饮的活性成分和作用靶点,结合Uniprot数据库对靶点进行标准化处理。采用Cytoscape 3.7.2软件绘制出祛痹痛风饮的活性成分–痛风靶点网络。通过GeneCards、OMIM、TTD、DRUGBANK数据库获得痛风的疾病靶点。将药物的作用靶点与疾病靶点进行交集,获得共同靶点。将交集靶点应用STRING数据库构建蛋白–蛋白相互作用网络图(PPI),通过DAVID数据库对共同靶点进行基因本体(GO)功能富集分析和京都基因与基因组百科全书(KEGG)通路富集分析,并将结果进行可视化处理。结果共预测到祛痹痛风饮中191个活性成分,87个与痛风共同的靶点。GO功能富集分析显示与炎症反应、细胞对脂多糖的应答、基因表达的正调控等相关。KEGG通路富集分析结果显示主要涉及Toll样受体信号通路、NOD样受体信号通路、NF-κB信号通路等方面。结论祛痹痛风饮可能通过促进尿酸排泄、抑制炎症因子的释放减轻、炎症反应发挥治疗痛风的作用,为深入研究祛痹痛风饮治疗痛风的作用机制提供了理论参考。     

Teaching Junior Medical Officers safe and effective prescribing

Medication errors are an iatrogenic threat to patient safety, and recently graduated Junior Medical Officers (JMOs) are a common source of these errors. A ward‐based, physician‐led, small‐group interactive teaching session was developed to improve JMOs competence in prescribing. The ability of JMOs to detect problems in mock medication charts before and after the teaching session was assessed, with the majority improving after the intervention, a result sustained on re‐testing later in the year. The teaching sessions were well received by JMOs.     

Chronic hepatitis C in the state prison system: insights into the problems and possible solutions

The prevalence of chronic hepatitis C virus (HCV) within the correctional system is estimated to be 10–20-times greater than that which is reported in the general population. High-risk behavioral patterns probably account for the greater estimates in this population. Recent observations of more than 780 patient-inmates infected with HCV within the California Department of Corrections suggest a very high prevalence of advanced fibrosis in this population. Observational studies performed in Texas have shown that the rates of chronic liver disease-related deaths have increased significantly between 1989 and 2003, especially among Hispanic patient-inmates. Viral hepatitis accounts for a significant number of these chronic liver disease-related deaths. Identification of high-risk patient-inmates infected with HCV, as well as appropriation of funds for their treatment, should result in a decreased rate of liver-related complications. This should translate into reduced morbidity and cost to correctional institutions, as well as to improved public health and safety.     

A Life‐Threatening Flecainide Overdose Treated with Intravenous Fat Emulsion

Flecainide is a Vaughan Williams Class Ic antidysrhythmic associated with PR, QRS, and QTc prolongation on the electrocardiogram and development of life‐threatening cardiac toxicity in overdose. The cornerstone of treatment is fluid resuscitation and the administration of magnesium and sodium bicarbonate. We report a case of flecainide overdose associated with life‐threatening hemodynamic compromise successfully treated with intravenous fat emulsion (IFE) therapy. IFE should be considered as a novel adjunctive therapy in patients with life‐threatening toxicity following flecainide overdose.