基于网络药理学的济脉通片降压机制研究

目的 采用网络药理学阐明济脉通片多成分-多靶点-多途径的作用理念，为进一步研究济脉通片降压药效物质基础和机制提供一定理论参考。方法 通过TCMSP数据库，结合口服利用度（≥ 30%）和类药性分析（≥ 0.18）参数，筛选济脉通片的活性成分；通过Drugbank和TCMSP数据库进行靶点预测分析；通过GENCARD数据库筛选出高血压疾病相关基因；结合DAVID和KEGG数据库进行GO分析和通路分析；使用Cystoscope软件构建"化合物-靶点-作用通路"网络图。结果 经筛选后得到济脉通片的33个化合物，148个潜在靶基因并映射到了223条信号通路，其中31条信号通路与高血压的发生发展密切相关，其中AGE-RAGE signaling pathway in diabetic complications、PI3K-Akt signaling pathway、TNFsignaling pathway、Adrenergic signaling in cardiomyocytes和Focal adhesion为重要的通路枢纽。结论 济脉通片主要通过多成分、多靶点、多通路调节血管内皮功能、炎症反应、钙钠离子转运、糖脂代谢等参与血管舒张、改善炎症、调节机体代谢、调节离子转运等而产生降压作用。     

Metabolism of deltamethrin and cis- and trans-permethrin by human expressed cytochrome P450 and carboxylesterase enzymes

1. The metabolism of the pyrethroids deltamethrin (DLM), cis-permethrin (CPM) and trans-permethrin (TPM) was studied in human expressed cytochrome P450 (CYP) and carboxylesterase (CES) enzymes.

2. DLM, CPM and TPM were metabolised by human CYP2B6 and CYP2C19, with the highest apparent intrinsic clearance (CL_int) values for pyrethroid metabolism being observed with CYP2C19. Other CYP enzymes contributing to the metabolism of one or more of the three pyrethroids were CYP1A2, CYP2C8, CYP2C9*1, CYP2D6*1, CYP3A4 and CYP3A5. None of the pyrethroids were metabolised by CYP2A6, CYP2E1, CYP3A7 or CYP4A11.

3. DLM, CPM and TPM were metabolised by both human CES1 and CES2 enzymes.

4. Apparent CL_int values for pyrethroid metabolism by CYP and CES enzymes were scaled to per gram of adult human liver using abundance values for microsomal CYP enzymes and for CES enzymes in liver microsomes and cytosol. TPM had the highest and CPM the lowest apparent CL_int values for total metabolism (CYP and CES enzymes) per gram of adult human liver.

5. Due to their higher abundance, all three pyrethroids were extensively metabolised by CES enzymes in adult human liver, with CYP enzymes only accounting for 2%, 10% and 1% of total metabolism for DLM, CPM and TPM, respectively.

     

The relationships among monocyte subsets,miRNAs and inflammatory cytokines in patients with acute myocardial infarction

Background

Acute myocardial infarction (AMI) causes irreversible myocardial damage and release of inflammatory mediators, including cytokines, chemokines and miRNAs. We aimed to investigate changes in the levels of cytokines (IL-6, TNF-α and IL-10), miRNAs profiles (miR-146 and miR-155) and distribution of different monocyte subsets (CD14++CD16-, CD14++CD16+, CD14+CD16++) in the acute and post-healing phases of AMI.

In Vitro-In Vivo Extrapolation and Hepatic Clearance-Dependent Underprediction

Accurately predicting the hepatic clearance of compounds using in vitro to in vivo extrapolation (IVIVE) is crucial within the pharmaceutical industry. However, several groups have recently highlighted the serious error in the process. Although empirical or regression-based scaling factors may be used to mitigate the common underprediction, they provide unsatisfying solutions because the reasoning behind the underlying error has yet to be determined. One previously noted trend was intrinsic clearance-dependent underprediction, highlighting the limitations of current in vitro systems. When applying these generated in vitro intrinsic clearance values during drug development and making first-in-human dose predictions for new chemical entities though, hepatic clearance is the parameter that must be estimated using a model of hepatic disposition, such as the well-stirred model. Here, we examine error across hepatic clearance ranges and find a similar hepatic clearance-dependent trend, with high clearance compounds not predicted to be so, demonstrating another gap in the field.     

Patients with Gastric Antral Vascular Ectasia (GAVE) Are at a Higher Risk of Gastrointestinal Bleeding in the Absence of Cirrhosis

Background and Aims: Gastric antral vascular ectasia (GAVE) is commonly found in patients with cirrhosis, but it is also associated with other diseases in the absence of cirrhosis. Whether GAVE confers a different severity of gastrointestinal (GI) bleeding between patients with and without cirrhosis remains unknown. We aim to examine whether there is a difference in clinically significant GI bleeding due to GAVE in patients with or without cirrhosis. Methods: This is a retrospective case-control study of patients who were diagnosed with GAVE between January 2000 and June 2014. Patients were categorized into cirrhosis and noncirrhosis groups, and those with an additional GI bleeding source were excluded. Univariate comparisons and multivariable models were constructed using logistic regression. Results: In total, 110 patients diagnosed with GAVE on esophagogastroduodenoscopy (EGD) were included in our analysis; 84 patients had cirrhosis (76.4%) and 26 (23.6%) did not. Active GI bleeding was more prevalent in patients without cirrhosis (63.4% vs. 32.1%, p=0.003) despite similar indications for EGD, and endoscopic treatment with argon plasma coagulation (APC) was required more often in this group, approaching statistical significance (27% vs. 10.7%, p=0.056). There was no difference in bleeding severity, as evidenced by similar re-bleeding rates, surgery, or death attributed to uncontrolled bleeding. The strongest independent risk factor for GI bleeding was the absence of cirrhosis (odds ratio (OR): 5.151 (95% confidence interval (CI): 1.08-24.48, p=0.039). Conclusions: Patients with GAVE in the absence of cirrhosis are at higher risk for active GI bleeding and require more frequent endoscopic treatment than similar patients with cirrhosis. It may be worthwhile to treat GAVE in this population even in the absence of active bleeding.     

黄石、荆门地区产妇母乳喂养自我效能影响因素分析

目的 探究黄石、荆门地区产后妇女母乳喂养自我效能的现状及影响因素,为改善母乳喂养率提供更多理论依据。方法 对2017年12月—2018年3月在湖北省黄石市、荆门市的三所医院住院分娩的产妇进行问卷调查,获得产妇社会人口特征、孕产相关资料、母乳喂养相关情况。采用多元线性回归分析母乳喂养自我效能的影响因素。结果 共1 023名产妇纳入分析,平均年龄(29.0±5.7)岁。已婚占98.3%,初产占54.0%,大专及以上学历占53.9%。研究对象的母乳喂养自我效能平均得分为(45.5±12.3)分。多元线性回归的结果显示:当前不存在乳腺问题(B=2.08,P=0.036)、有母乳喂养经历(B=3.62,P<0.001)、家人提供母乳喂养指导或经验(B=3.20,P=0.001)、丈夫支持母乳喂养(B=5.87,P=0.001)及产后30 min内有医护母乳喂养帮助(B=3.02,P=0.003)的产妇母乳喂养自我效能得分更高。结论 产后妇女的母乳喂养自我效能可能与其健康状况、母乳喂养经历、社会支持及母乳喂养卫生服务有关。应对产后妇女提供广泛的社会支持,加强母乳喂养卫生服务提供,以提高其母乳喂养的自我效能,促进母乳喂养。     

Serum growth factor stability in different eye drop packaging systems during storage

Serum eye drops (SED) have shown beneficial effects in patients suffering from dry eye syndrome and are manufactured for an increasing number of patients in Australia every year. Previous studies have examined the stability of serum growth factors during storage in either experimental vessels not used as the final packaging system or in eye drop bottles. To ensure the quality and safety of SED product manufactured in Australia, the stability of growth factors in serum packaged into two different systems during storage at different temperatures was examined. Healthy blood donors provided a whole blood donation, from which serum was prepared, diluted to 20% and dispensed into either a tube or a vial packaging system. The stability of growth factors, fibronectin and total protein in tube segments was comparable to matched vials samples during storage at −30 °C, 4 °C, 22 °C and 37 °C, with the exception of EGF and fibronectin in 20% SED stored in tube segments, which were more sensitive to storage conditions at 4 °C and 22 °C when compared to vials. Additionally, the growth factor, fibronectin and total protein concentration in both tube segments and vials was stable during storage at −30 °C for at least 9 months. This study highlights the impact of different manufacturing procedures on serum growth factor stability during storage.     

Early onset scoliosis and current treatment methods

ObjectiveProvide an update of the management options for early onset scoliosis patients, including general assessment, conservative and surgical options.MethodsWe included the updated information about the assessment and management options of Early Onset Scoliosis, taking into consideration the non-fusion methods, including the burden on the patient and their family.ResultsWith the heterogeneity of this population, it is difficult to get a consensus about a unified protocol for management. Accordingly, the surgeon dealing with these cases needs to be aware of the broad range of surgical and non-surgical methods when treating these patients.ConclusionThe main aim of early onset scoliosis treatment is to gain a flexible spine associated with normal lung development and thoracic growth. Management needs to be individualized between the surgeon and patient in relation to the etiology and patient conditions.